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1.
Int J Nanomedicine ; 19: 3031-3044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562612

RESUMO

Purpose: Peripheral nerve damage lacks an appropriate diagnosis consistent with the patient's symptoms, despite expensive magnetic resonance imaging or electrodiagnostic assessments, which cause discomfort. Ultrasonography is valuable for diagnosing and treating nerve lesions; however, it is unsuitable for detecting small lesions. Poly(vanillin-oxalate) (PVO) nanoparticles are prepared from vanillin, a phytochemical with antioxidant and anti-inflammatory properties. Previously, PVO nanoparticles were cleaved by H2O2 to release vanillin, exert therapeutic efficacy, and generate CO2 to increase ultrasound contrast. However, the role of PVO nanoparticles in peripheral nerve lesion models is still unknown. Herein, we aimed to determine whether PVO nanoparticles can function as contrast and therapeutic agents for nerve lesions. Methods: To induce sciatic neuritis, rats were administered a perineural injection of carrageenan using a nerve stimulator under ultrasonographic guidance, and PVO nanoparticles were injected perineurally to evaluate ultrasonographic contrast and therapeutic effects. Reverse transcription-quantitative PCR was performed to detect mRNA levels of pro-inflammatory cytokines, ie, tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2. Results: In the rat model of sciatic neuritis, PVO nanoparticles generated CO2 bubbles to increase ultrasonographic contrast, and a single perineural injection of PVO nanoparticles suppressed the expression of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2, reduced the expression of F4/80, and increased the expression of GAP43. Conclusion: The results of the current study suggest that PVO nanoparticles could be developed as ultrasonographic contrast agents and therapeutic agents for nerve lesions.


Assuntos
Benzaldeídos , Nanopartículas , Neuropatia Ciática , Ratos , Humanos , Animais , Peróxido de Hidrogênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Dióxido de Carbono , Ciclo-Oxigenase 2/metabolismo , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Nanopartículas/química , Nervo Isquiático/diagnóstico por imagem , Nervo Isquiático/metabolismo
2.
J Biotechnol ; 386: 19-27, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38521166

RESUMO

Vanillin is a valuable natural product that can be used as a fragrance and additive. Recent research in the biosynthesis of vanillin has brought attention to a key enzyme, carboxylic acid reductase (CAR), which catalyzes the reduction of vanillic acid to vanillin. Nevertheless, the biosynthesis of vanillin is hampered by the low activity and stability of CAR. As such, a rational design campaign was conducted on a well-documented carboxylic acid reductase from Segniliparus rugosus (SrCAR), using vanillic acid as the model substrate. After combined active site saturation and iterative site-specific mutagenesis, the best quadruple mutant N292H/K524S/A627L/E1121W (M3) was successfully obtained. In comparison to the wildtype SrCAR, M3 demonstrated a 4.2-fold increase in catalytic efficiency (kcat/Km), and its half-life (t1/2) was enhanced by 3.8 times up to 385.08 minutes at 40 °C. In silico docking and molecular dynamics simulation provided insights into the improved activity and stability. In the subsequent preparative-scale reaction with 100 mM (16.8 g L-1) vanillic acid, the whole cell catalysis utilizing M3 produced 10.15 g·L-1 of vanillin and 1.11 g·L-1 of vanillyl alcohol, respectively. This work demonstrates a dual improvement in the activity and thermal stability of SrCAR, thereby potentially facilitating the application of carboxylic acid reductase in the biosynthesis of vanillin.


Assuntos
Oxirredutases , Ácido Vanílico , Oxirredutases/química , Benzaldeídos
3.
Bioresour Technol ; 398: 130517, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437961

RESUMO

The utilization of lignin, an abundant and renewable bio-aromatic source, is of significant importance. In this study, lignin oxidation was examined at different temperatures with zirconium oxide (ZrO2)-supported nickel (Ni), cobalt (Co) and bimetallic Ni-Co metal catalysts under different solvents and oxygen pressure. Non-catalytic oxidation reaction produced maximum bio-oil (35.3 wt%), while catalytic oxidation significantly increased the bio-oil yield. The bimetallic catalyst Ni-Co/ZrO2 produced the highest bio-oil yield (67.4 wt%) compared to the monometallic catalyst Ni/ZrO2 (59.3 wt%) and Co/ZrO2 (54.0 wt%). The selectively higher percentage of vanillin, 2-methoxy phenol, acetovanillone, acetosyringone and vanillic acid compounds are found in the catalytic bio-oil. Moreover, it has been observed that the bimetallic Co-Ni/ZrO2 produced a higher amount of vanillin (43.7% and 13.30 wt%) compound. These results demonstrate that the bimetallic Ni-Co/ZrO2 catalyst promotes the selective cleavage of the ether ß-O-4 bond in lignin, leading to a higher yield of phenolic monomer compounds.


Assuntos
Benzaldeídos , Cobalto , Níquel , Óxidos , Óleos de Plantas , Polifenóis , Zircônio , Lignina , Fenóis
4.
An Acad Bras Cienc ; 96(1): e20220875, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511740

RESUMO

Compounds with a pyrazoline scaffold are useful as sensors for fluorescence detection of different types of analytes. Recovery of a pyrazoline-based sensor with a view to use it recurrently would be more facile when the sensing molecule is attached to a solid support. A reaction sequence has been designed to synthesize two benzaldehyde-pyrazoline hybrids as examples of a hitherto unknown type of compounds to be employed for the potential derivatization of polymers containing primary amino groups through azomethine formation. All intermediates, including the fairly unstable N1 -unsubstituted pyrazolines, along with the target compounds have been structurally characterized, with an emphasis on their particular NMR features. Examination of the photophysical properties of these benzaldehyde-pyrazoline hybrids showed that, despite the shortening of the extended N1-N2-C3 conjugated system common to 1,3,5-triarylpyrazolines through the replacement of the aryl at N1 by an aryloxyacetyl moiety, the novel compounds exhibit emission maxima at approximately 350 nm. Moreover, the introduction of a moderately electron-withdrawing substituent such as chlorine in the phenyl at C3 of pyrazoline leads to an amplification of fluorescence intensity.


Assuntos
Benzaldeídos , Polímeros , Pirazóis/química , Espectroscopia de Ressonância Magnética , Corantes
5.
Microb Biotechnol ; 17(3): e14448, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38498302

RESUMO

Pseudomonas putida is a soil bacterium with multiple uses in fermentation and biotransformation processes. P. putida ATCC 12633 can biotransform benzaldehyde and other aldehydes into valuable α-hydroxyketones, such as (S)-2-hydroxypropiophenone. However, poor tolerance of this strain toward chaotropic aldehydes hampers efficient biotransformation processes. To circumvent this problem, we expressed the gene encoding the global regulator PprI from Deinococcus radiodurans, an inducer of pleiotropic proteins promoting DNA repair, in P. putida. Fine-tuned gene expression was achieved using an expression plasmid under the control of the LacIQ /Ptrc system, and the cross-protective role of PprI was assessed against multiple stress treatments. Moreover, the stress-tolerant P. putida strain was tested for 2-hydroxypropiophenone production using whole resting cells in the presence of relevant aldehyde substrates. P. putida cells harbouring the global transcriptional regulator exhibited high tolerance toward benzaldehyde, acetaldehyde, ethanol, butanol, NaCl, H2 O2 and thermal stress, thereby reflecting the multistress protection profile conferred by PprI. Additionally, the engineered cells converted aldehydes to 2-hydroxypropiophenone more efficiently than the parental P. putida strain. 2-Hydroxypropiophenone concentration reached 1.6 g L-1 upon a 3-h incubation under optimized conditions, at a cell concentration of 0.033 g wet cell weight mL-1 in the presence of 20 mM benzaldehyde and 600 mM acetaldehyde. Product yield and productivity were 0.74 g 2-HPP g-1 benzaldehyde and 0.089 g 2-HPP g cell dry weight-1 h-1 , respectively, 35% higher than the control experiments. Taken together, these results demonstrate that introducing PprI from D. radiodurans enhances chaotrope tolerance and 2-HPP production in P. putida ATCC 12633.


Assuntos
Deinococcus , Hidroxipropiofenona , Pseudomonas putida , Benzaldeídos/metabolismo , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Deinococcus/genética , Acetaldeído/metabolismo
6.
J Agric Food Chem ; 72(12): 6471-6480, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38462720

RESUMO

Increasing consumer aversion to non-natural flavoring substances is prompting a heightened interest in enzymatic processes for flavor production. This includes methylation reactions, which are often performed by using hazardous chemicals. By correlation of aroma profile data and transcriptomic analysis, a novel O-methyltransferase (OMT) catalyzing a respective reaction within the formation of p-anisaldehyde was identified in the mushroom Pleurotus sapidus. Heterologous expression in E. coli followed by purification allowed for further characterization of the enzyme. Besides p-hydroxybenzaldehyde, the proposed precursor of p-anisaldehyde, the enzyme catalyzed the methylation of further hydroxylated aromatic compounds at the meta- and para-position. The Km values determined for p-hydroxybenzaldehyde and S-adenosyl-l-methionine were 80 and 107 µM, respectively. Surprisingly, the studied enzyme enabled the transmethylation of thiol-nucleophiles, as indicated by the formation of 2-methyl-3-(methylthio)furan from 2-methyl-3-furanthiol. Moreover, the enzyme was crystallized at a resolution of 2.0 Å, representing the first published crystal structure of a basidiomycetous OMT.


Assuntos
Benzaldeídos , Metiltransferases , Pleurotus , Metiltransferases/metabolismo , Escherichia coli/metabolismo , Pleurotus/metabolismo
7.
J Agric Food Chem ; 72(12): 6463-6470, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38501643

RESUMO

Eugenol, the main component of essential oil from the Syzygium aromaticum clove tree, has great potential as an alternative bioresource feedstock for biosynthesis purposes. Although eugenol degradation to ferulic acid was investigated, an efficient method for directly converting eugenol to targeted natural products has not been established. Herein we identified the inherent inhibitions by simply combining the previously reported ferulic acid biosynthetic pathway and vanillin biosynthetic pathway. To overcome this, we developed a novel biosynthetic pathway for converting eugenol into vanillin, by introducing cinnamoyl-CoA reductase (CCR), which catalyzes conversion of coniferyl aldehyde to feruloyl-CoA. This approach bypasses the need for two catalysts, namely coniferyl aldehyde dehydrogenase and feruloyl-CoA synthetase, thereby eliminating inhibition while simplifying the pathway. To further improve efficiency, we enhanced CCR catalytic efficiency via directed evolution and leveraged an artificialvanillin biosensor for high-throughput screening. Switching the cofactor preference of CCR from NADP+ to NAD+ significantly improved pathway efficiency. This newly designed pathway provides an alternative strategy for efficiently biosynthesizing feruloyl-CoA-derived natural products using eugenol.


Assuntos
Acil Coenzima A , Benzaldeídos , Vias Biossintéticas , Ácidos Cumáricos , Eugenol , Eugenol/metabolismo
8.
Acta Biomater ; 178: 68-82, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38452962

RESUMO

Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.


Assuntos
Benzaldeídos , Catecóis , Hidrogéis , Úlceras Orais , Humanos , Ratos , Animais , Hidrogéis/farmacologia , Adesivos , Qualidade de Vida , Materiais Biocompatíveis , Inflamação , Antibacterianos/farmacologia
9.
Arch Insect Biochem Physiol ; 115(2): e22091, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38385805

RESUMO

Insects are covered with free neutral cuticular hydrocarbons (CHC) that may be linear, branched, and unsaturated and vary in their chain length. The CHC composition is species-specific and contributes to the adaptation of the animal to its ecological niche. Commonly, CHCs contribute substantially to the inward and outward barrier function of the cuticle and serve pheromonal communication. They are generally determined by gas-chromatography, a time-consuming method requiring detailed expertize, but it is not available in many laboratories. Here, we report on the establishment of a colorimetric method allowing semi-quantitative determination of unsaturated CHCs in Drosophila flies. This method is based on the in vitro reaction of vanillin with double bounds in lipid molecules in an acidic solution to generate a reddish color. We found a robust correlation between gas chromatographic and vanillin-colorimetric data on unsaturated CHCs amounts in single flies. As the role of unsaturated CHCs in the performance of insects in their environment is only partly understood, we think that this novel method would allow fast and broad analyses of this type of CHCs in insects both in the field and in laboratories and thereby contribute to a substantial improvement in the investigation of this matter.


Assuntos
Colorimetria , Drosophila , Animais , Benzaldeídos , Lipídeos
10.
Water Res ; 253: 121222, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38335841

RESUMO

The emergence and transmission of antibiotic resistance genes (ARGs) through plasmid-mediated conjugation has become a significant worldwide public health threat. Biofilms are widely recognized as the primary reservoirs for ARGs, providing favorable conditions for horizontal gene transfer. Quorum sensing (QS) plays a critical role in bacterial biofilm formation, which further influences the spread of bacterial resistance. In this study, we examined the effects of vanillin, a QS inhibitor (QSI), at subinhibitory concentrations (sub-MICs) ranging from 0 - 0.1 g/L, on the transfer of ARGs between Escherichia coli and Pseudomonas aeruginosa. Our findings indicated that vanillin at sub-MICs inhibited the conjugative transfer frequency of the RP4 plasmid. This inhibition was supported by the downregulation of plasmid transfer genes. The suppression of conjugation can mainly be attributed to the inhibition of biofilm formation, the synthesis of extracellular polymeric substances (EPS), and the secretion of virulence factors, all of which are regulated by the bacterial QS system. On the other hand, the levels of ROS and cell membrane permeability were not primary explanations for this phenomenon. Furthermore, vanillin also reduced the conjugative transfer frequency of ARGs in wastewater effluent, providing a potential approach to alleviate bacterial resistance in water environments. These findings underscore the regulatory role of QSI in controlling ARGs transfer and have significant implications for manipulating the dissemination of bacterial resistance in the environment.


Assuntos
Antibacterianos , Benzaldeídos , Percepção de Quorum , Antibacterianos/farmacologia , Genes Bacterianos , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Escherichia coli , Plasmídeos , Transferência Genética Horizontal
11.
Bioresour Technol ; 397: 130507, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423483

RESUMO

Major challenge in biorefineries is the use of all lignocellulosic components, particularly lignins. In this study, Thermobacillus xylanilyliticus grew on kraft lignin, steam-exploded and native wheat straws produced different sets of phenoloxidases and xylanases, according to the substrate. After growth, limited lignin structural modifications, mainly accompanied by a decrease in phenolic acids was observed by Nuclear Magnetic Resonance spectroscopy. The depletion of p-coumaric acid, vanillin and p-hydroxybenzaldehyde combined to vanillin production in the culture media indicated that the bacterium can transform some phenolic compounds. Proteomic approaches allowed the identification of 29 to 33 different hemicellulases according to the substrates. Twenty oxidoreductases were differentially expressed between kraft lignin and steam-exploded wheat straw. These oxidoreductases may be involved in lignin and aromatic compound utilization and detoxification. This study highlights the potential value of Thermobacillus xylanilyticus and its enzymes in the simultaneous valorization of hemicellulose and phenolic compounds from lignocelluloses.


Assuntos
Bacillales , Benzaldeídos , Lignina , Monofenol Mono-Oxigenase , Lignina/química , Vapor , Proteômica , Fenóis , Triticum/química
12.
Int J Biol Macromol ; 262(Pt 1): 130024, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340931

RESUMO

The water-soluble chitosan derivative (WSCD) was made by mixing chitosan with sodium hydroxide, treating the mixture with chloroacetic acid, and then forming a Schiff base with vanillin in an acidic medium. In this study, we examined the corrosion-inhibiting ability of a WSCD on mild steel surfaces in acidic environments. Weight loss, EIS, PDP, LPS, and OCP measurements were used to study the corrosion resistance on mild steel surfaces in 1 M HCl solutions with known concentrations of WSCD. The results show that WSCD functions effectively as a mixed-type anodic and cathodic inhibitor, providing 87 % corrosion inhibition efficiency at 75 ppm. Using SEM to investigate the morphology of corroded mild steel with and without varying amounts of WSCD, impedance measurements show the development of a thin film of inhibitor on the metal surface, the extent of which increases as the inhibitor concentration rises. The WSCD molecule first adsorbs on mild steel and follows Langmuir adsorption isotherm. It is found that the (∆Gads0)adsorption's free energy is -17.473 kJ/mol. The contact angle measurements confirm that the hydrophobicity of the metal surface has increased as a result of the inhibitor's thin film development.


Assuntos
Benzaldeídos , Quitosana , Aço , Corrosão , Água , Propriedades de Superfície , Ácidos
13.
Plant Physiol Biochem ; 207: 108427, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38367389

RESUMO

Fluorescent materials and technologies have become widely used in scientific research, and due to the ability to convert light wavelengths, their application to photosynthetic organisms can affect their development by altering light quality. However, the impacts of fluorescent materials on aquatic plants and their environmental risks remain unclear. To assess the effects of luminescent materials on floating aquatic macrophytes and their rhizosphere microorganisms, 4-(di-p-tolylamino)benzaldehyde-A (DTB-A) and 4-(di-p-tolylamino)benzaldehyde-M (DTB-M) (emitting blue-green and orange-red light, respectively) were added individually and jointly to Spirodela polyrhiza cultures and set at different concentrations (1, 10, and 100 µM). Both DTB-A and DTB-M exhibited phytotoxicity, which increased with concentration under separate treatment. Moreover, the combined group exhibited obvious stress relief at 10 µM compared to the individually treated group. Fluorescence imaging showed that DTB-A and DTB-M were able to enter the cell matrix and organelles of plant leaves and roots. Peroxidation induced cellular damage, contributing to a decrease in superoxide dismutase (SOD) and peroxidase (POD) activities and malondialdehyde (MDA) accumulation. Decomposition of organelle structures, starch accumulation in chloroplasts, and plasmolysis were observed under the ultrastructure, disrupting photosynthetic pigment content and photosynthesis. DTB-A and DTB-M exposure resulted in growth inhibition, dry weight loss, and leaf yellowing in S. polyrhiza. A total of 3519 Operational Taxonomic Units (OTUs) were identified in the rhizosphere microbiome. The microbial communities were dominated by Alphaproteobacteria, Oxyphotobacteria, and Gammaproteobacteria, with the abundance and diversity varied significantly among treatment groups according to Shannon, Simpson, and Chao1 indices. This study revealed the stress defense response of S. polyrhiza to DTB-A and DTB-M exposures, which provides a broader perspective for the bioremediation of pollutants using aquatic plants and supports the further development of fluorescent materials for applications.


Assuntos
Araceae , Benzaldeídos , Benzaldeídos/farmacologia , Fotossíntese , Antioxidantes/metabolismo , Cloroplastos/metabolismo , Luz , Plantas/metabolismo , Araceae/fisiologia
14.
Expert Opin Pharmacother ; 25(2): 157-170, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344818

RESUMO

INTRODUCTION: Sickle cell disease (SCD) is an inherited disorder characterised by polymerisation of deoxygenated haemoglobin S and microvascular obstruction. The cardinal feature is generalised pain referred to as vaso-occlusive crises (VOC), multi-organ damage and premature death. SCD is the most prevalent inherited life-threatening disorders in the world and over 85% of world's 400,000 annual births occur low-and-middle-income countries. Hydroxyurea remained the only approved disease modifying therapy (1998) until the FDA approved L-glutamine (2017), Crizanlizumab and Voxelotor (2019) and gene therapies (Exa-cel and Lovo-cel, 2023). AREAS COVERED: Clinical trials performed in the last 10 years (November 2013 - November 2023) were selected for the review. They were divided according to the mechanisms of drug action. The following pubmed central search terms [sickle cell disease] or [sickle cell anaemia] Hydroxycarbamide/ Hydroxyurea, L-Glutamine, Voxelotor, Crizanlizumab, Mitapivat, Etavopivat, gene therapy, haematopoietic stem cell transplantation, and combination therapy. EXPERT OPINION: We recommend future trials of combination therapies for specific complications such as VOCs, chronic pain and renal impairment as well as personalised medicine approach based on phenotype and patient characteristics. Following recent approval of gene therapy for SCD, the challenge is addressing the role of shared decision-making with families, global access and affordability.


Assuntos
Anemia Falciforme , Benzaldeídos , Dor Crônica , Pirazinas , Pirazóis , Humanos , Hidroxiureia/uso terapêutico , Glutamina/uso terapêutico , Anemia Falciforme/tratamento farmacológico , Dor Crônica/tratamento farmacológico , Combinação de Medicamentos
15.
Appl Environ Microbiol ; 90(3): e0215523, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38380926

RESUMO

Emergent strategies to valorize lignin, an abundant but underutilized aromatic biopolymer, include tandem processes that integrate chemical depolymerization and biological catalysis. To date, aromatic monomers from C-O bond cleavage of lignin have been converted to bioproducts, but the presence of recalcitrant C-C bonds in lignin limits the product yield. A promising chemocatalytic strategy that overcomes this limitation involves phenol methyl protection and autoxidation. Incorporating this into a tandem process requires microbial cell factories able to transform the p-methoxylated products in the resulting methylated lignin stream. In this study, we assessed the ability of Rhodococcus jostii RHA1 to catabolize the major aromatic products in a methylated lignin stream and elucidated the pathways responsible for this catabolism. RHA1 grew on a methylated pine lignin stream, catabolizing the major aromatic monomers: p-methoxybenzoate (p-MBA), veratrate, and veratraldehyde. Bioinformatic analyses suggested that a cytochrome P450, PbdA, and its cognate reductase, PbdB, are involved in p-MBA catabolism. Gene deletion studies established that both pbdA and pbdB are essential for growth on p-MBA and several derivatives. Furthermore, a deletion mutant of a candidate p-hydroxybenzoate (p-HBA) hydroxylase, ΔpobA, did not grow on p-HBA. Veratraldehyde and veratrate catabolism required both vanillin dehydrogenase (Vdh) and vanillate O-demethylase (VanAB), revealing previously unknown roles of these enzymes. Finally, a ΔpcaL strain grew on neither p-MBA nor veratrate, indicating they are catabolized through the ß-ketoadipate pathway. This study expands our understanding of the bacterial catabolism of aromatic compounds and facilitates the development of biocatalysts for lignin valorization.IMPORTANCELignin, an abundant aromatic polymer found in plant biomass, is a promising renewable replacement for fossil fuels as a feedstock for the chemical industry. Strategies for upgrading lignin include processes that couple the catalytic fractionation of biomass and biocatalytic transformation of the resulting aromatic compounds with a microbial cell factory. Engineering microbial cell factories for this biocatalysis requires characterization of bacterial pathways involved in catabolizing lignin-derived aromatic compounds. This study identifies new pathways for lignin-derived aromatic degradation in Rhodococcus, a genus of bacteria well suited for biocatalysis. Additionally, we describe previously unknown activities of characterized enzymes on lignin-derived compounds, expanding their utility. This work advances the development of strategies to replace fossil fuel-based feedstocks with sustainable alternatives.


Assuntos
Lignina , Rhodococcus , Lignina/metabolismo , Benzaldeídos/metabolismo , Rhodococcus/genética , Rhodococcus/metabolismo
16.
J Enzyme Inhib Med Chem ; 39(1): 2313055, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38416868

RESUMO

Toll-like receptor (TLR) innate immunity signalling protects against pathogens, but excessive or prolonged signalling contributes to a range of inflammatory conditions. Structural information on the TLR cytoplasmic TIR (Toll/interleukin-1 receptor) domains and the downstream adaptor proteins can help us develop inhibitors targeting this pathway. The small molecule o-vanillin has previously been reported as an inhibitor of TLR2 signalling. To study its mechanism of action, we tested its binding to the TIR domain of the TLR adaptor MAL/TIRAP (MALTIR). We show that o-vanillin binds to MALTIR and inhibits its higher-order assembly in vitro. Using NMR approaches, we show that o-vanillin forms a covalent bond with lysine 210 of MAL. We confirm in mouse and human cells that o-vanillin inhibits TLR2 but not TLR4 signalling, independently of MAL, suggesting it may covalently modify TLR2 signalling complexes directly. Reactive aldehyde-containing small molecules such as o-vanillin may target multiple proteins in the cell.


Assuntos
Benzaldeídos , Lisina , Receptor 2 Toll-Like , Humanos , Animais , Camundongos , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Receptores Toll-Like/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores de Interleucina-1/metabolismo
17.
Appetite ; 195: 107236, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38307298

RESUMO

OBJECTIVE: The study aimed to assess potential effects of vaping on individual taste and smell perception in a sample of young adult New Zealanders. DESIGN: This cross-sectional study measured taste and smell perception using intensity and hedonic ratings to two olfactory (i.e., vanillin, methional) and two gustatory stimuli (i.e., sucrose, monosodium glutamate), representing sweet and savoury flavours. Detection sensitivities to sucrose and vanillin were also assessed using a forced choice detection paradigm aligned with the signal detection framework. MANCOVAs were employed to compare sensory perception between groups based on vaping use frequency. Additional regression analyses were conducted to identify potential predictors of intensity and hedonic sensory ratings. SETTING: Participants were recruited from the University of Otago student population and surrounding neighbourhoods of Dunedin, New Zealand in 2023. PARTICIPANTS: The study included 213 university students (98 vapers and 115 non-vapers) RESULTS: We found a significant difference in hedonic ratings for vanillin, indicating a stronger preference among non-vapers. However, no other differences between the two groups were significant. Notably, the use of tobacco and mint flavours were emerged as significant predictors for hedonic responses to the savoury smell and sweet taste stimulus, respectively. No significant differences were observed between groups in the ability to detect weak stimuli. CONCLUSIONS: Our findings suggest that vape use, particularly with specific flavours, may be associated with alterations in hedonic responses to smells. This finding may have potential implications for how vaping affects on food preferences and dietary choices.


Assuntos
Olfato , Percepção Gustatória , Vaping , Humanos , Adulto Jovem , População Australasiana , Benzaldeídos , Estudos Transversais , Aromatizantes , Preferências Alimentares/fisiologia , Nova Zelândia , Olfato/fisiologia , Sacarose , Percepção Gustatória/fisiologia
18.
Molecules ; 29(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338351

RESUMO

Sweet potato provides rich nutrients and bioactive substances for the human diet. In this study, the volatile organic compounds of five pigmented-fleshed sweet potato cultivars were determined, the characteristic aroma compounds were screened, and a correlation analysis was carried out with the aroma precursors. In total, 66 volatile organic compounds were identified. Terpenoids and aldehydes were the main volatile compounds, accounting for 59% and 17%, respectively. Fifteen compounds, including seven aldehydes, six terpenes, one furan, and phenol, were identified as key aromatic compounds for sweet potato using relative odor activity values (ROAVs) and contributed to flower, sweet, and fat flavors. The OR sample exhibited a significant presence of trans-ß-Ionone, while the Y sample showed high levels of benzaldehyde. Starch, soluble sugars, 20 amino acids, and 25 fatty acids were detected as volatile compounds precursors. Among them, total starch (57.2%), phenylalanine (126.82 ± 0.02 g/g), and fatty acids (6.45 µg/mg) were all most abundant in Y, and LY contained the most soluble sugar (14.65%). The results of the correlation analysis revealed the significant correlations were identified between seven carotenoids and trans-ß-Ionone, soluble sugar and nerol, two fatty acids and hexanal, phenylalanine and 10 fatty acids with benzaldehyde, respectively. In general, terpenoids and aldehydes were identified as the main key aromatic compounds in sweet potatoes, and carotenoids had more influence on the aroma of OR than other cultivars. Soluble sugars, amino acids, and fatty acids probably serve as important precursors for some key aroma compounds in sweet potatoes. These findings provide valuable insights for the formation of sweet potato aroma.


Assuntos
Ipomoea batatas , Norisoprenoides , Solanum tuberosum , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Benzaldeídos , Ipomoea batatas/química , Carotenoides , Odorantes/análise , Terpenos , Aldeídos/análise , Açúcares , Ácidos Graxos , Fenilalanina , Amido
19.
Food Res Int ; 180: 114057, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395574

RESUMO

The inhibitory effects of amino acids and their combinations on the formation of heterocyclic amines were investigated in this study. The great potential in the inhibition of HAs was observed in amino acid combinations compared with that of single agents. At a mass ratio of 1:1, a His-Pro combination achieved a maximum inhibitory rate of 80 %, and the total HAs content decreased to 4.70 ± 0.18 ng/g relative to the control (24.49 ± 2.18 ng/g). However, the inhibitory rate of triple combinations showed no obvious increase compared with the binary combinations. Benzaldehyde, phenylacetaldehyde, methylglyoxal, and glyoxal were positively correlated with HAs formation, and His-Pro combination (1:4) led to a significant reduction of benzaldehyde and phenylacetaldehyde at scavenging rates of 79 % and 92 %. Thus, the synergistic inhibition was achieved by simultaneously scavenging these aldehyde intermediates, and other inhibitory target, such as competition with precursors and elimination of final products can serve as supporting factors. These results provide a new perspective for approaches to enhance the suppression of HAs and control the formation of flavor compounds.


Assuntos
Acetaldeído/análogos & derivados , Aminoácidos , Compostos Heterocíclicos , Animais , Bovinos , Benzaldeídos , Aminas/química
20.
Int Immunopharmacol ; 129: 111657, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38335655

RESUMO

BACKGROUND: Epilepsy is a severe neurological disorder associated with substantial morbidity and mortality. Vanillin (Van) is a natural phenolic aldehyde with beneficial pharmacological properties. This study investigated the neuroprotective effects of Van in epilepsy and elucidated its mechanism of action. METHODS: Swiss albino mice were divided into the following five groups: "normal group", 0.9 % saline; "pentylenetetrazole (PTZ) group", intraperitoneal administration of 35 mg/kg PTZ on alternate days up to 42 days; and "PTZ + Van 20", "PTZ + Van 40", and "PTZ + sodium valproate (Val)" groups received PTZ injections in conjunction withVan 20 mg, Van 40 mg/kg, and Val 300 mg/kg, respectively. Behavioural tests and hippocampal histopathological analysis were performed in all groups. The Nrf2/HO-1/NQO1 and HMGB1/RAGE/TLR4/NFκB pathways, oxidative stress, neuro-inflammation, and apoptotic markers were analysed. Furthermore, brain acetylcholinesterase (AChE) activity and levels of dopamine (DA), gamma-aminobutyric acid GABA, and serotonin 5-HT were assessed. RESULTS: Van prolonged seizure manifestations and improved electroencephalogram (EEG)criteriain conjunction with 100 mg/kg PTZ once daily. Van administration increased Nrf2/HO-1/NQO1 levels, with subsequent attenuation of malondialdehyde (MDA) and nitric oxide (NO) levels with elevated glutathione (GSH) levels and intensified superoxide dismutase (SOD) and catalase activities. Van reduced the gene and protein expression of HMGB1/RAGE/TLR4/NFκB and decreased the levels of inflammatory and apoptotic markers. In addition, Van reduced AChE activity, and elevated glial fibrillary acidic proteins (GFAP) increased neurotransmitter and brain-derived neurotrophic factors (BDNF). CONCLUSION: By increasing Nrf2/HO-1/NQO1 levels and downregulating the HMGB1/RAGE/TLR4/ NFκB pathway, Van offered protection in PTZ-kindled mice with subsequent attenuation in lipid peroxidation, upregulation in antioxidant enzyme activities, and reduction in inflammation and apoptosis.


Assuntos
Benzaldeídos , Epilepsia , Proteína HMGB1 , Camundongos , Animais , Pentilenotetrazol , Fator 2 Relacionado a NF-E2/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteína HMGB1/metabolismo , Acetilcolinesterase/metabolismo , Epilepsia/induzido quimicamente , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Estresse Oxidativo , Transtornos da Memória , Glutationa/metabolismo , Inflamação
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