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1.
Food Chem ; 462: 140947, 2025 Jan 01.
Article de Anglais | MEDLINE | ID: mdl-39208736

RÉSUMÉ

Excess nitrites are potentially threatening to human health, so it is urgent to develop accurate and sensitive methods. The development of sensors can provide early warning of possible hazards and alert people to protect public health. This work presents an NiSx@MoS2-composite with excellent electrochemical activity, representing a key finding for highly sensitive NO2- detection and sensor development. With the assistance of NiSx@MoS2, this electrochemical sensor has excellent quantitative detection performance. It has a wide detection range (0.0001-0.0020 mg/mL) and a low detection limit (1.863*10-5 mg/mL) for NO2-. This electrochemical sensor maintains excellent specificity among numerous interferences, and it completes the accurate detection of different real food samples. Pleasingly, the electrochemical sensor has satisfactory repeatability stability, and potential for practical applications. It would demonstrate tremendous potential in scientific dietary guidance, food safety detection and other fields.


Sujet(s)
Disulfures , Techniques électrochimiques , Limite de détection , Molybdène , Molybdène/composition chimique , Techniques électrochimiques/instrumentation , Disulfures/composition chimique , Nitrites/analyse , Contamination des aliments/analyse
2.
J Nanobiotechnology ; 22(1): 596, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39354525

RÉSUMÉ

Early diagnosis and treatment of gastric cancer (GC) play a vital role in improving efficacy, reducing mortality and prolonging patients' lives. Given the importance of early detection of gastric cancer, an electrochemical biosensor was developed for the ultrasensitive detection of miR-19b-3p by integrating MoS2-based nanozymes, hybridization chain reaction (HCR) with enzyme catalyzed reaction. The as-prepared MoS2-based nanocomposites were used as substrate materials to construct nanoprobes, which can simultaneously load probe DNA and HCR initiator for signal amplification. Moreover, the MoS2-based nanocomposites are also employed as nanozymes to amplify electrochemical response. The presence of miR-19b-3p induced the assembly of MoS2-based nanoprobes on the electrode surface, which can activate in-situ HCR reaction to load a large number of horseradish peroxidase (HRP) for signal amplification. Coupling with the co-catalytic ability of HRP and MoS2-based nanozymes, the designed electrochemical biosensor can detect as low as 0.7 aM miR-19b-3p. More importantly, this biosensor can efficiently analyze miR-19b-3p in clinical samples from healthy people and gastric cancer patients due to its excellent sensitivity and selectivity, suggesting that this biosensor has a potential application in early diagnosis of disease.


Sujet(s)
Techniques de biocapteur , Disulfures , Techniques électrochimiques , Horseradish peroxidase , microARN , Molybdène , Tumeurs de l'estomac , Tumeurs de l'estomac/diagnostic , Humains , microARN/génétique , Molybdène/composition chimique , Techniques électrochimiques/méthodes , Horseradish peroxidase/composition chimique , Horseradish peroxidase/métabolisme , Techniques de biocapteur/méthodes , Disulfures/composition chimique , Hybridation d'acides nucléiques , Nanocomposites/composition chimique , Limite de détection
3.
Appl Microbiol Biotechnol ; 108(1): 478, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39354113

RÉSUMÉ

Microbial transglutaminase (MTG) from Streptomyces mobaraensis is widely used in the food and pharmaceutical industries for cross-linking and post-translational modification of proteins. It is believed that its industrial applications could be further broadened by improving its thermostability. In our previous study, we showed that the introduction of structure-based disulfide bonds improved the thermostability of MTG, and we succeeded in obtaining a thermostable mutant, D3C/G283C, with a T50 (incubation temperature at which 50% of the initial activity remains) 9 °C higher than that of wild-type MTG. In this study, we performed random mutations using D3C/G283C as a template and found several amino acid substitutions that contributed to the improvement of thermostability, and investigated a thermostable mutant (D3C/S101P/G157S/G250R/G283C) with three amino acid mutations in addition to the disulfide bond. The T50 of this mutant was 10 °C higher than that of the wild type, the optimal temperature for enzymatic reaction was increased to 65 °C compared to 50 °C for the wild type, and the catalytic efficiency (kcat/Km) at 37.0 °C was increased from 3.3 × 102 M-1 s-1 for the wild type to 5.9 × 102 M-1 s-1. X-ray crystallography of the D3C/G283C MTG showed no major structural differences against wild-type MTG. Structural differences were found that may contribute to thermostabilization and improve catalytic efficiency. KEY POINTS: • Improved heat resistance is essential to broaden the application of MTG. • The MTG mutant D3C/S101P/G157S/G250R/G283C showed improved thermostability. • X-ray crystallography of the disulfide bridge mutant D3C/G283C MTG was elucidated.


Sujet(s)
Disulfures , Stabilité enzymatique , Streptomyces , Transglutaminases , Streptomyces/enzymologie , Streptomyces/génétique , Transglutaminases/génétique , Transglutaminases/composition chimique , Transglutaminases/métabolisme , Disulfures/composition chimique , Disulfures/métabolisme , Substitution d'acide aminé , Mutagenèse , Température élevée , Température , Protéines bactériennes/génétique , Protéines bactériennes/composition chimique , Protéines bactériennes/métabolisme , Cinétique
4.
Proc Natl Acad Sci U S A ; 121(42): e2409672121, 2024 Oct 15.
Article de Anglais | MEDLINE | ID: mdl-39378083

RÉSUMÉ

The assembly of ß-barrel proteins into membranes is mediated by the evolutionarily conserved ß-barrel assembly machine (BAM) complex. In Escherichia coli, BAM folds numerous substrates which vary considerably in size and shape. How BAM is able to efficiently fold such a diverse array of ß-barrel substrates is not clear. Here, we develop a disulfide crosslinking method to trap native substrates in vivo as they fold on BAM. By placing a cysteine within the luminal wall of the BamA barrel as well as in the substrate ß-strands, we can compare the residence time of each substrate strand within the BamA lumen. We validated this method using two defective, slow-folding substrates. We used this method to characterize stable intermediates which occur during folding of two structurally different native substrates. Strikingly, these intermediates occur during identical stages of folding for both substrates: soon after folding has begun and just before folding is completed. We suggest that these intermediates arise due to barriers to folding that are common between ß-barrel substrates, and that the BAM catalyst is able to fold so many different substrates because it addresses these common challenges.


Sujet(s)
Protéines de la membrane externe bactérienne , Protéines Escherichia coli , Escherichia coli , Pliage des protéines , Protéines Escherichia coli/métabolisme , Protéines Escherichia coli/composition chimique , Escherichia coli/métabolisme , Protéines de la membrane externe bactérienne/composition chimique , Protéines de la membrane externe bactérienne/métabolisme , Modèles moléculaires , Disulfures/composition chimique , Disulfures/métabolisme , Spécificité du substrat , Cystéine/composition chimique , Cystéine/métabolisme
5.
Mikrochim Acta ; 191(11): 662, 2024 10 10.
Article de Anglais | MEDLINE | ID: mdl-39387898

RÉSUMÉ

An electrochemical biosensor was created to identify the liver cancer marker alpha-fetoprotein (AFP) by employing nanocomposite materials. A combination of reduced graphene oxide (rGO) and molybdenum disulfide (MoS2) was selected as the substrate material for the sensor to prepare the PtNPs/MoS2@rGO electrochemical immunosensor. Among them, rGO has strong conductivity and MoS2 provides a large surface area for the anchoring of PtNPs for better attachment to the hybridized nanomaterials. Meanwhile, PtNPs exhibit consistent biocompatibility and excellent electrocatalytic activity. PtNPs also attach to hybrid nanomaterials and bind the antibody via the Pt-S bond, thereby furnishing the antibody with multiple binding sites for enhanced antibody adhesion. The immunosensor achieved ultra-sensitive AFP detection by exploiting the specific antigen-antibody binding. The structure and morphology of the PtNPs/MoS2@rGO composites were investigated by transmission electron microscopy (TEM), energy dispersive X-ray (EDS) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy, and the sensor was electrochemically characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, using differential pulse voltammetry the biosensor detected AFP in serum within a linear range of 1 ~ 105 pg/mL, with a correlation coefficient (r2) of 0.9989, and a detection limit of 0.12 pg/mL (S/N = 3). The method offers a new approach for the ultrasensitive detection of serum AFP and is extremely selective, accurate, and precise with a relative standard deviation (RSD) of less than 6%. It has been successfully applied to the analysis of real human blood samples.


Sujet(s)
Techniques de biocapteur , Disulfures , Techniques électrochimiques , Graphite , Limite de détection , Nanoparticules métalliques , Molybdène , Platine , Alphafoetoprotéines , Humains , Alphafoetoprotéines/analyse , Alphafoetoprotéines/immunologie , Molybdène/composition chimique , Graphite/composition chimique , Platine/composition chimique , Techniques électrochimiques/méthodes , Disulfures/composition chimique , Techniques de biocapteur/méthodes , Dosage immunologique/méthodes , Nanoparticules métalliques/composition chimique , Anticorps immobilisés/immunologie , Anticorps immobilisés/composition chimique , Nanocomposites/composition chimique
6.
J Nanobiotechnology ; 22(1): 587, 2024 Sep 28.
Article de Anglais | MEDLINE | ID: mdl-39342211

RÉSUMÉ

Spatiotemporally controlled cargo release is a key advantage of nanocarriers in anti-tumor therapy. Various external or internal stimuli-responsive nanomedicines have been reported for their ability to increase drug levels at the diseased site and enhance therapeutic efficacy through a triggered release mechanism. Redox-manipulating nanocarriers, by exploiting the redox imbalances in tumor tissues, can achieve precise drug release, enhancing therapeutic efficacy while minimizing damage to healthy cells. As a typical redox-sensitive bond, the disulfide bond is considered a promising tool for designing tumor-specific, stimulus-responsive drug delivery systems (DDS). The intracellular redox imbalance caused by tumor microenvironment (TME) regulation has emerged as an appealing therapeutic target for cancer treatment. Sustained glutathione (GSH) depletion in the TME by redox-manipulating nanocarriers can exacerbate oxidative stress through the exchange of disulfide-thiol bonds, thereby enhancing the efficacy of ROS-based cancer therapy. Intriguingly, GSH depletion is simultaneously associated with glutathione peroxidase 4 (GPX4) inhibition and dihydrolipoamide S-acetyltransferase (DLAT) oligomerization, triggering mechanisms such as ferroptosis and cuproptosis, which increase the sensitivity of tumor cells. Hence, in this review, we present a comprehensive summary of the advances in disulfide based redox-manipulating nanocarriers for anticancer drug delivery and provide an overview of some representative achievements for combinational therapy and theragnostic. The high concentration of GSH in the TME enables the engineering of redox-responsive nanocarriers for GSH-triggered on-demand drug delivery, which relies on the thiol-disulfide exchange reaction between GSH and disulfide-containing vehicles. Conversely, redox-manipulating nanocarriers can deplete GSH, thereby enhancing the efficacy of ROS-based treatment nanoplatforms. In brief, we summarize the up-to-date developments of the redox-manipulating nanocarriers for cancer therapy based on DDS and provide viewpoints for the establishment of more stringent anti-tumor nanoplatform.


Sujet(s)
Antinéoplasiques , Vecteurs de médicaments , Systèmes de délivrance de médicaments , Nanoparticules , Tumeurs , Oxydoréduction , Humains , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Vecteurs de médicaments/composition chimique , Animaux , Systèmes de délivrance de médicaments/méthodes , Tumeurs/traitement médicamenteux , Nanoparticules/composition chimique , Microenvironnement tumoral/effets des médicaments et des substances chimiques , Glutathion/métabolisme , Glutathion/composition chimique , Disulfures/composition chimique , Espèces réactives de l'oxygène/métabolisme , Stress oxydatif/effets des médicaments et des substances chimiques , Libération de médicament
7.
Int J Mol Sci ; 25(18)2024 Sep 11.
Article de Anglais | MEDLINE | ID: mdl-39337289

RÉSUMÉ

Single-domain antibodies, including variable domains of the heavy chains of heavy chain-only antibodies (VHHs) from camelids and variable domains of immunoglobulin new antigen receptors (VNARs) from cartilaginous fish, show the therapeutic potential of targeting antigens in a cytosol reducing environment. A large proportion of single-domain antibodies contain non-canonical cysteines and corresponding non-canonical disulfide bonds situated on the protein surface, rendering them vulnerable to environmental factors. Research on non-canonical disulfide bonds has been limited, with a focus solely on VHHs and utilizing only cysteine mutations rather than the reducing agent treatment. In this study, we examined an anti-lysozyme VNAR and an anti-BC2-tag VHH, including their non-canonical disulfide bond reduced counterparts and non-canonical cysteine mutants. Both the affinity and stability of the VNARs and VHHs decreased in the non-canonical cysteine mutants, whereas the reduced-state samples exhibited decreased thermal stability, with their affinity remaining almost unchanged regardless of the presence of reducing agents. Molecular dynamics simulations suggested that the decrease in affinity of the mutants resulted from increased flexibility of the CDRs, the disappearance of non-canonical cysteine-antigen interactions, and the perturbation of other antigen-interacting residues caused by mutations. These findings highlight the significance of non-canonical cysteines for the affinity of single-domain antibodies and demonstrate that the mutation of non-canonical cysteines is not equivalent to the disruption of non-canonical disulfide bonds with a reducing agent when assessing the function of non-canonical disulfide bonds.


Sujet(s)
Cystéine , Disulfures , Simulation de dynamique moléculaire , Anticorps à domaine unique , Cystéine/composition chimique , Cystéine/métabolisme , Disulfures/composition chimique , Animaux , Anticorps à domaine unique/composition chimique , Anticorps à domaine unique/immunologie , Anticorps à domaine unique/métabolisme , Stabilité protéique , Récepteurs aux antigènes/composition chimique , Récepteurs aux antigènes/métabolisme , Récepteurs aux antigènes/génétique , Récepteurs aux antigènes/immunologie , Affinité des anticorps , Chaines lourdes des immunoglobulines/composition chimique , Chaines lourdes des immunoglobulines/génétique , Chaines lourdes des immunoglobulines/métabolisme , Lysozyme/composition chimique , Lysozyme/métabolisme , Lysozyme/immunologie , Région variable d'immunoglobuline/composition chimique , Région variable d'immunoglobuline/génétique , Mutation
8.
Luminescence ; 39(9): e4884, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39258707

RÉSUMÉ

In present work, synthesis of a nanohybrid material using Fe and MoS2 has been performed via a cost-effective and environmentally friendly route for sustainable manufacturing innovation. Rice straw extract was prepared and used as a reducing and chelating agent to synthesize the nanohybrid material by mixing it with molybdenum disulfide (MoS2) and ferric nitrate [Fe (NO3)3.9H2O], followed by heating and calcination. The X-ray diffraction (XRD) pattern confirms the formation of a nanohybrid consisting of monoclinic Fe2(MoO4)3, cubic Fe2.957O4, and orthorhombic FeS with 86% consisting of Fe2(MoO4)3. The properties were analyzed through Fourier-transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results of the dynamic light scattering (DLS) study revealed a heterogeneous size distribution, with an average particle size of 48.42 nm for 18% of particles and 384.54 nm for 82% of particles. Additionally, the zeta potential was measured to be -18.88 mV, suggesting moderate stability. X-ray photoelectron spectroscopy (XPS) results confirmed the presence of both Fe2+ and Fe3+ oxidation states along with the presence of Molybdenum (Mo), oxygen (O), and Sulphur (S). The prepared nanohybrid material exhibited a band gap of 2.95 eV, and the photoluminescence intensity increased almost twice that of bare MoS2. The present work holds potential applications in photo luminescent nanoplatform for biomedical applications.


Sujet(s)
Disulfures , Technologie de la chimie verte , Molybdène , Oryza , Taille de particule , Molybdène/composition chimique , Disulfures/composition chimique , Oryza/composition chimique , Fer/composition chimique , Propriétés de surface
9.
PLoS One ; 19(9): e0310166, 2024.
Article de Anglais | MEDLINE | ID: mdl-39255261

RÉSUMÉ

This study demonstrates the use of computational methods to simulate the molecular dynamics involved in hemoglobin concentration sensing, utilizing Material Studio and the TCAD Silvaco device simulator. A non-invasive and flexible Graphene/MoS2 heterostructure has been proposed for sensing hemoglobin concentration in blood samples. The findings reveal a notable shift in the wavelength-dependent refractive index and extinction coefficient, as well as significant changes in the absorption coefficient and reflectivity of the Graphene/MoS2 heterostructure in response to different hemoglobin concentrations, specifically within an approximate range of 0.3 µm to 1 µm. Moreover, the spectral response of the heterostructure demonstrates that at a particular wavelength of approximately 600 nm, a maximum response is obtained. This wavelength can be considered optimal for detecting various levels of hemoglobin using this heterostructure. The anticipated outcome is a comprehensive understanding of the fundamental principles, ultimately resulting in the development of an exceptionally sensitive platform for detecting hemoglobin concentration.


Sujet(s)
Disulfures , Graphite , Hémoglobines , Molybdène , Graphite/composition chimique , Hémoglobines/analyse , Hémoglobines/composition chimique , Molybdène/composition chimique , Humains , Disulfures/composition chimique , Disulfures/sang , Simulation de dynamique moléculaire , Techniques de biocapteur/méthodes , Techniques de biocapteur/instrumentation
10.
Nat Commun ; 15(1): 7799, 2024 Sep 06.
Article de Anglais | MEDLINE | ID: mdl-39242578

RÉSUMÉ

Peptides are valuable for therapeutic development, with multicyclic peptides showing promise in mimicking antigen-binding potency of antibodies. However, our capability to engineer multicyclic peptide scaffolds, particularly for the construction of large combinatorial libraries, is still limited. Here, we study the interplay of disulfide pairing between three biscysteine motifs, and designed a range of triscysteine motifs with unique disulfide-directing capability for regulating the oxidative folding of multicyclic peptides. We demonstrate that incorporating these motifs into random sequences allows the design of disulfide-directed multicyclic peptide (DDMP) libraries with up to four disulfide bonds, which have been applied for the successful discovery of peptide binders with nanomolar affinity to several challenging targets. This study encourages the use of more diverse disulfide-directing motifs for creating multicyclic peptide libraries and opens an avenue for discovering functional peptides in sequence and structural space beyond existing peptide scaffolds, potentially advancing the field of peptide drug discovery.


Sujet(s)
Cystéine , Disulfures , Banque de peptides , Disulfures/composition chimique , Cystéine/composition chimique , Motifs d'acides aminés , Découverte de médicament/méthodes , Séquence d'acides aminés , Peptides/composition chimique , Peptides/métabolisme , Peptides cycliques/composition chimique , Peptides cycliques/métabolisme , Liaison aux protéines , Humains , Oxydoréduction , Pliage des protéines
11.
Cells ; 13(17)2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39273052

RÉSUMÉ

The complex structure of monoclonal antibodies (mAbs) expressed in Chinese hamster ovary (CHO) cells may result in the accumulation of unfolded proteins, triggering endoplasmic reticulum (ER) stress and an unfolded protein response (UPR). If the protein folding ability cannot maintain ER homeostasis, the cell will shut down protein translation and ultimately induce apoptosis. We co-overexpressed HsQSOX1b and survivin proteins in the antibody-producing cell line CHO-PAb to obtain a new cell line, CHO-PAb-QS. Compared with CHO-PAb cells, the survival time of CHO-PAb-QS cells in batch culture was extended by 2 days, and the antibody accumulation and productivity were increased by 52% and 45%, respectively. The proportion of (HC-LC)2 was approximately doubled in the CHO-PAb-QS cells, which adapted to the accelerated disulfide bond folding capacity by upregulating the UPR's strength and increasing the ER content. The results of the apoptosis assays indicated that the CHO-PAb-QS cell line exhibited more excellent resistance to apoptosis induced by ER stress. Finally, CHO-PAb-QS cells exhibited mild oxidative stress but did not significantly alter the redox status. This study demonstrated that strategies based on HsQSOX1b and survivin co-overexpression could facilitate protein disulfide bond folding and anti-apoptosis ability, enhancing antibody production efficiency in CHO cell lines.


Sujet(s)
Apoptose , Cricetulus , Disulfures , Pliage des protéines , Cellules CHO , Animaux , Disulfures/métabolisme , Disulfures/composition chimique , Stress du réticulum endoplasmique , Réponse aux protéines mal repliées , Production d'anticorps , Anticorps monoclonaux , Cricetinae , Survivine/métabolisme , Humains , Réticulum endoplasmique/métabolisme , Stress oxydatif
12.
Anal Chim Acta ; 1325: 343090, 2024 Oct 09.
Article de Anglais | MEDLINE | ID: mdl-39244300

RÉSUMÉ

BACKGROUND: Curcumin has been used in traditional medicine because of its pharmacological activity, including antioxidant, antibacterial, anticancer, and anticarcinogenic properties. Therefore, sensitive and selective monitoring of curcumin is highly demand for practical application. RESULTS: In this study, we describe the construction of a fluorescence method for curcumin assay based on nitrogen-doped MoS2 quantum dots (N-MoS2 QDs). The N-MoS2 QDs are constructed by a solvothermal method using sodium molybdate and Cys as precursors. With the addition of curcumin, the bright blue fluorescence of N-MoS2 QDs is quenched by the inner filter effect (IFE). The QDs emitted bright blue fluorescence and could be quenched by the addition of curcumin via IFE. The dynamic range is the range of 0.1-10 µM for curcumin detection, with a detection limit of 59 nM. N-MoS2 QDs were applied for curcumin assay in real samples with good recovery. In addition, the N-MoS2 QDs exhibited relative low cytotoxicity and could be applied for fluorescence-based imaging in biological samples. SIGNIFICANCE: Our study indicates that the sensor possesses good selectivity to monitor curcumin in water samples, human urine samples, ginger powder samples, mustard samples, and curry samples with satisfactory recoveries. The N-MoS2 QDs possess less cytotoxicity with excellent biocompatibility and were applied for in vitro cell imaging.


Sujet(s)
Curcumine , Disulfures , Colorants fluorescents , Molybdène , Azote , Boîtes quantiques , Curcumine/composition chimique , Curcumine/pharmacologie , Boîtes quantiques/composition chimique , Molybdène/composition chimique , Humains , Disulfures/composition chimique , Colorants fluorescents/composition chimique , Colorants fluorescents/synthèse chimique , Azote/composition chimique , Imagerie optique , Limite de détection , Spectrométrie de fluorescence , Survie cellulaire/effets des médicaments et des substances chimiques
13.
J Agric Food Chem ; 72(37): 20658-20669, 2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39226125

RÉSUMÉ

Sulfur-containing compounds have diverse biological functions and are crucial in crop protection chemistry. In this study, a series of novel 1-methyl-1H-pyrazol-5-amine derivatives incorporating disulfide moieties were synthesized and evaluated for their antimicrobial properties. In vitro bioassays demonstrated that compound 7f displayed potent antifungal activity against Valsa mali, with an EC50 value of 0.64 mg/L, outperforming allicin (EC50 = 26.0 mg/L) but lower than tebuconazole (EC50 = 0.33 mg/L). In vivo experiments confirmed that compound 7f could effectively inhibit V. mali infection on apples at a concentration of 100 mg/L, similar to the positive control tebuconazole. Mechanistic studies revealed that compound 7f could induce hyphal shrinkage and collapse, trigger intracellular reactive oxygen species accumulation, modulate antioxidant enzyme activities, initiate lipid peroxidation, and ultimately cause irreversible oxidative damage to the cells of V. mali. Additionally, compound 7b exhibited notable antibacterial activity, particularly against Pseudomonas syringae pv. actinidiae, with a MIC90 value of 1.56 mg/L, surpassing the positive controls allicin, bismerthiazol, and streptomycin sulfate. These findings suggest that 1-methyl-1H-pyrazol-5-amine derivatives containing disulfide moieties hold promise as potent candidates for the development of novel antimicrobial agents.


Sujet(s)
Disulfures , Tests de sensibilité microbienne , Pyrazoles , Disulfures/composition chimique , Disulfures/pharmacologie , Pyrazoles/pharmacologie , Pyrazoles/composition chimique , Pyrazoles/synthèse chimique , Maladies des plantes/microbiologie , Relation structure-activité , Pseudomonas syringae/effets des médicaments et des substances chimiques , Antibactériens/pharmacologie , Antibactériens/composition chimique , Antibactériens/synthèse chimique , Anti-infectieux/pharmacologie , Anti-infectieux/composition chimique , Anti-infectieux/synthèse chimique , Structure moléculaire , Fongicides industriels/pharmacologie , Fongicides industriels/composition chimique , Fongicides industriels/synthèse chimique
14.
J Agric Food Chem ; 72(37): 20299-20307, 2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39231265

RÉSUMÉ

Microorganisms are the most common cause of food spoilage. Pseudomonas aeruginosa is a common foodborne pathogen that causes food spoilage and poses a serious threat to food safety. As a crucial target in antitoxicity strategies, the quorum sensing (QS) system shows promising potential for further development. The garlic extract diallyl disulfide exhibits inhibitory activity against the QS system of P. aeruginosa, with disulfide bonds serving as the active component. However, the biological activity of other symmetric disulfides has not been investigated in this capacity. The study synthesized 39 disulfide bond-containing analogs and evaluated their activity as quorum sensing inhibitors (QSIs). The results showed that p-hydroxyphenyl substitution can replace the allyl groups while maintaining strong biological activity. The virulence factors production was reduced by compound 2i, with the strongest inhibitory effect being observed on elastase production. Synergistic inhibition was observed in the presence of antibiotics like ciprofloxacin and tobramycin. 2i successfully inhibited P. aeruginosa infection in the Galleria mellonella larvae model. Primary mechanism studies using transcriptome, surface plasmon resonance and molecular docking suggested that 2i inhibits the QS system by targeting the LasR protein. Thus, compound 2i could be used in developing QSIs for the control of P. aeruginosa infections.


Sujet(s)
Antibactériens , Disulfures , Ail , Extraits de plantes , Pseudomonas aeruginosa , Détection du quorum , Détection du quorum/effets des médicaments et des substances chimiques , Pseudomonas aeruginosa/effets des médicaments et des substances chimiques , Ail/composition chimique , Disulfures/composition chimique , Disulfures/pharmacologie , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Antibactériens/pharmacologie , Antibactériens/composition chimique , Animaux , Papillons de nuit/effets des médicaments et des substances chimiques , Papillons de nuit/microbiologie , Simulation de docking moléculaire , Relation structure-activité , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Protéines bactériennes/composition chimique , Infections à Pseudomonas/traitement médicamenteux , Infections à Pseudomonas/microbiologie
15.
Molecules ; 29(17)2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39275071

RÉSUMÉ

Oligonucleotide drugs are shining in clinical therapeutics, but efficient and safe delivery systems severely limit their widespread use. A disulfide unit technology platform based on dynamic thiol exchange chemistry at the cell membrane has the potential for drug delivery. However, the alteration of the disulfide unit CSSC dihedral angle induced by different substituents directly affects the effectiveness of this technology and its stability. Previously, we constructed a trivalent low dihedral angle disulfide unit that can effectively promote the cellular uptake of small molecules. Here, we constructed a novel disulfide unit-masked oligonucleotide hybrid based on a low dihedral angle disulfide unit, motivated by prodrug design. Cellular imaging results showed that such a system exhibited superior cellular delivery efficiency than the commercial Lipo2000 without cytotoxicity. The thiol reagents significantly reduced its cellular uptake (57-74%), which proved to be endocytosis-independent. In addition, in vivo distribution experiments in mice showed that such systems can be rapidly distributed in liver tissues with a duration of action of more than 24 h, representing a potential means of silencing genes involved in the pathogenesis of liver-like diseases. In conclusion, this trivalent disulfide unit-masked system we constructed can effectively deliver large oligonucleotide drugs.


Sujet(s)
Disulfures , Oligonucléotides , Disulfures/composition chimique , Animaux , Oligonucléotides/composition chimique , Souris , Humains , Systèmes de délivrance de médicaments , Foie/métabolisme , Foie/effets des médicaments et des substances chimiques
16.
Nanotechnology ; 35(49)2024 Sep 27.
Article de Anglais | MEDLINE | ID: mdl-39293467

RÉSUMÉ

Effective drug delivery with precise tumour targeting is crucial for cancer treatment. To address the challenges posed by the specificity and complexity of the tumour microenvironment, we developed a poly(tetraethylene glycol)-based disulfide nanoparticle (NP) platform and explored its potential in cancer treatment, focusing on drug loading and controlled release performance. Poly(tetraethylene glycol) NPs were characterised using nuclear magnetic resonance spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Additionally, we evaluated physicochemical properties, including dynamic light scattering, zeta potential analysis, drug loading capacity (DLC), and drug loading efficiency (DLE). The impact of NPs on the mouse colorectal cancer cell line (CT26) and NIH3T3 cells was assessed using a cytotoxicity assay, live/dead staining assay, flow cytometry, and confocal fluorescence microscopy. The experimental results align with the expected chemical structure and physicochemical properties of poly(tetraethylene glycol) NPs. These NPs exhibit high DLE (78.7%) and DLC (12%), with minimal changes in particle size over time in different media.In vitroexperiments revealed that the NPs can induce significant cytotoxicity and apoptosis in CT26 cells. Cellular uptake notably increases with increasing concentration and exposure time. The confocal microscopic analysis confirmed the effective distribution and accumulation of NPs within cells. In conclusion, poly(tetraethylene glycol) NPs hold promise for improving drug-delivery efficiency, offering potential advancements in cancer treatment.


Sujet(s)
Nanoparticules , Oxydoréduction , Polyéthylène glycols , Polyéthylène glycols/composition chimique , Souris , Animaux , Concentration en ions d'hydrogène , Nanoparticules/composition chimique , Lignée cellulaire tumorale , Cellules NIH 3T3 , Apoptose/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Vecteurs de médicaments/composition chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Taille de particule , Disulfures/composition chimique
17.
ACS Nano ; 18(39): 26961-26974, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39305262

RÉSUMÉ

The application of enzyme-like molybdenum disulfide (MoS2) in tissue repair was confronted with stable dispersion, solubilization, and biotoxicity. Here, the injectable self-healing hydrogel was successfully designed using a step-by-step coassembly of chitosan and MoS2. Polyphenolic chitosan as a "structural stabilizer" of MoS2 nanosheets reconstructed well-dispersed MoS2@CSH nanosheets, which improved the biocompatibility of traditional MoS2, and strengthened its photothermal conversion and enzyme-like activities, guaranteeing highly efficient radical scavenging and antimicrobial properties. Furthermore, the polyphenol chitosan was employed again as a "molecular cross-linking agent" to form the injectable NIR-responsive MoS2@CSH hydrogel by accelerating hydrogen-bond interaction among chitosan and the multicross-linking reaction among polyphenols. The rapid self-healing ability was conducive to wound closure and dynamic adaptability. An experimental study on infected wound healing demonstrated that MoS2@CSH hydrogel could substantially eradicate bacteria and accelerate the angiogenesis of infected wounds. The photothermal-driven coassembly of MoS2 and polycation provided an alternative strategy for infected wound healing.


Sujet(s)
Chitosane , Disulfures , Hydrogels , Molybdène , Cicatrisation de plaie , Molybdène/composition chimique , Molybdène/pharmacologie , Chitosane/composition chimique , Chitosane/pharmacologie , Disulfures/composition chimique , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Hydrogels/composition chimique , Hydrogels/pharmacologie , Animaux , Souris , Antibactériens/pharmacologie , Antibactériens/composition chimique , Nanostructures/composition chimique , Staphylococcus aureus/effets des médicaments et des substances chimiques , Humains , Tests de sensibilité microbienne , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie
18.
Int J Biol Macromol ; 279(Pt 4): 135467, 2024 Nov.
Article de Anglais | MEDLINE | ID: mdl-39270898

RÉSUMÉ

In order to improve the dispersion of molybdenum disulfide (MoS2) and enhance the performance of MoS2, two alginate-derived biomass carbon-MoS2 (BC-MoS2) composites: CMB/CMS, were prepared by introducing BC during the synthesis of MoS2 by hydrothermal. The effects of different gels, times and temperatures of the synthesized BC-MoS2 were investigated, and the adsorption capacity for methylene blue (MB), basic fuchsin (BF) and copper ions (Cu2+) was tested. The results indicated that the vertical growth of MoS2 on the BC surface could be realized when using xero-gel, while the BC and MoS2 were mixed uniformly when using wet-gel. Compared with MoS2, the hydrophilicity and water dispersibility of BC-MoS2 were greatly improved, and BC-MoS2 had better adsorption capacity for MB/BF/Cu2+ (99.61/86.83/60 mg/g). The adsorption mechanism exhibits that the adsorption force of BC-MoS2 on MB/BF is mainly based on the electrostatic force, and the adsorption on Cu2+ comes from the electrostatic force and the Lewis soft-soft interaction. This study dramatically enriches the application of transition metal chalcogenides and provides a meaningful reference for wastewater treatment.


Sujet(s)
Alginates , Biomasse , Carbone , Disulfures , Molybdène , Eaux usées , Purification de l'eau , Molybdène/composition chimique , Disulfures/composition chimique , Alginates/composition chimique , Adsorption , Eaux usées/composition chimique , Purification de l'eau/méthodes , Carbone/composition chimique , Nanostructures/composition chimique , Cuivre/composition chimique , Polluants chimiques de l'eau/composition chimique , Polluants chimiques de l'eau/isolement et purification
19.
Chemosphere ; 365: 143334, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39278325

RÉSUMÉ

The current study tries to find the impact of the integration of laccase enzyme (Lac) onto magnetized chitosan (Cs) nanoparticles composed of molybdenum disulfide (MoS2 NPs) (Fe3O4/Cs/MoS2/Lac NPs) on the removal of AFM1 in milk samples. The Fe3O4/Cs/MoS2/Lac NPs were characterized by FT-IR, XRD, BET, TEM, FESEM, EDS, PSA, and VSM analysis. The cytotoxic activity of the synthesized nanoparticles in different concentrations was evaluated using the MTT method. The results show that the synthesized nanoparticles don't have cytotoxic activity at concentrations less than 20 mg/l. The ability of the prepared nanoparticles to remove AFM1 was compared by bare laccase enzyme, MoS2, and Fe3O4/Cs/MoS2 composite, indicating that the Fe3O4/Cs/MoS2/Lac NPs the highest adsorption efficiency toward AFM1. Besides, the immobilization efficiency of laccase with a concentration range of 0.5-2.0 was investigated, indicating that the highest activity recovery of 96.8% was obtained using 2 mg/ml laccase loading capacity. The highest removal percentage of AFM1 (68.5%) in the milk samples was obtained by the Fe3O4/Cs/MoS2/Lac NPs at a contact time of 1 h. As a result, Fe3O4/MoS2/Cs/Lac NPs can potentially be utilized as an effective sorbent with high capacity and selectivity to remove AFM1 from milk samples.


Sujet(s)
Aflatoxine M1 , Chitosane , Disulfures , Laccase , Lait , Molybdène , Nanocomposites , Chitosane/composition chimique , Laccase/métabolisme , Laccase/composition chimique , Lait/composition chimique , Molybdène/composition chimique , Animaux , Nanocomposites/composition chimique , Aflatoxine M1/composition chimique , Disulfures/composition chimique , Adsorption , Contamination des aliments/analyse
20.
J Environ Sci Health B ; 59(9): 595-610, 2024.
Article de Anglais | MEDLINE | ID: mdl-39287337

RÉSUMÉ

Toxic intermediates in food caused by chloramphenicol (CP) and furazolidone (FZ) have gained interest in research toward their detection. Hence, fast, reliable, and accurate detection of CP and FZ in food products is of utmost importance. Here, a novel molybdenum disulfide-connected carbon nanotube aerogel/poly (3,4-ethylenedioxythiophene) [MoS2/CNTs aerogel/PEDOT] nanocomposite materials are constructed and deposited on the pretreated carbon paste electrode (PCPE) by a facile eletropolymerization method. The characterization of MoS2/CNTs aerogel/PEDOT nanocomposite was analyzed by scanning electron microscopy (SEM), cyclic voltammetry, and differential pulse voltammetry. The modified MoS2/CNTs aerogel/PEDOT nanocomposite has improved sensing characteristics for detecting CP and FZ in PBS solution. For this work, we have studied various parameters like electrocatalytic activity, the effect of scan rates, pH variation studies, and concentration variation studies. Under optimum conditions, the modified electrode exhibited superior sensing ability compared to the bare and pretreated CPE. This improvement in electrocatalytic activity can be the higher conductivity, larger surface area, increased heterogeneous rate constant, and presence of more active sites in the MoS2/CNTs aerogel/PEDOT nanocomposite. The modified electrode demonstrated distinct electrochemical sensing toward the individual and simultaneous analysis of CP and FZ with a high sensitivity of 0.701 µA. µM-1 .cm-2 for CP and 0.787 µA. µM-1 .cm-2 for FZ and a low detection limit of 3.74 nM for CP and 3.83 nM for FZ with good reproducibility, repeatability, and interferences. Additionally, the prepared sensor effectively detects CP and FZ in food samples (honey and milk) with an acceptable recovery range and a relative standard deviation below 4%.


Sujet(s)
Composés hétérocycliques bicycliques , Chloramphénicol , Disulfures , Techniques électrochimiques , Contamination des aliments , Furazolidone , Molybdène , Nanocomposites , Nanotubes de carbone , Polymères , Chloramphénicol/analyse , Furazolidone/analyse , Nanocomposites/composition chimique , Nanotubes de carbone/composition chimique , Techniques électrochimiques/instrumentation , Techniques électrochimiques/méthodes , Contamination des aliments/analyse , Polymères/composition chimique , Disulfures/composition chimique , Composés hétérocycliques bicycliques/composition chimique , Molybdène/composition chimique , Antibactériens/analyse , Limite de détection , Lait/composition chimique
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