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1.
Neoplasma ; 71(3): 243-254, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38958714

RESUMO

Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.


Assuntos
Proliferação de Células , Dissulfetos , Ferroptose , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Espécies Reativas de Oxigênio , Ácidos Sulfínicos , Humanos , Ferroptose/efeitos dos fármacos , Dissulfetos/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Proliferação de Células/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Movimento Celular/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Glutationa/metabolismo , Sobrevivência Celular/efeitos dos fármacos
2.
Sci Rep ; 14(1): 15054, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956159

RESUMO

This study aimed to develop a highly efficient nanocomposite composed of magnetic chitosan/molybdenum disulfide (CS/MoS2/Fe3O4) for the removal of three polycyclic aromatic hydrocarbons (PAHs)-pyrene, anthracene, and phenanthrene. Novelty was introduced through the innovative synthesis procedure and the utilization of magnetic properties for enhanced adsorption capabilities. Additionally, the greenness of chitosan as a sorbent component was emphasized, highlighting its biodegradability and low environmental impact compared to traditional sorbents. Factors influencing PAH adsorption, such as nanocomposite dosage, initial PAH concentration, pH, and contact time, were systematically investigated and optimized. The results revealed that optimal removal efficiencies were attained at an initial PAH concentration of 150 mg/L, a sorbent dose of 0.045 g, pH 6.0, and a contact time of 150 min. The pseudo-second-order kinetic model exhibited superior fitting to the experimental data, indicating an equilibrium time of approximately 150 min. Moreover, the equilibrium adsorption process followed the Freundlich isotherm model, with kf and n values exceeding 7.91 mg/g and 1.20, respectively. Remarkably, the maximum absorption capacities for phenanthrene, anthracene, and pyrene on the sorbent were determined as 217 mg/g, 204 mg/g, and 222 mg/g, respectively. These findings underscore the significant potential of the CS/MoS2/Fe3O4 nanocomposite for efficiently removing PAHs from milk and other dairy products, thereby contributing to improved food safety and public health.


Assuntos
Quitosana , Dissulfetos , Leite , Molibdênio , Nanocompostos , Hidrocarbonetos Policíclicos Aromáticos , Dissulfetos/química , Nanocompostos/química , Quitosana/química , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Molibdênio/química , Leite/química , Animais , Adsorção , Cinética , Concentração de Íons de Hidrogênio
3.
PeerJ ; 12: e17742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39035169

RESUMO

Background: Allicin, a bioactive compound derived from garlic (Allium sativum), demonstrates antibacterial activity against a broad spectrum of bacteria including the most common meningitis pathogens. In order to advocate for allicin as a potential therapeutic candidate for bacterial meningitis, the present study aimed to assess the ability of allicin to cross the blood-brain barrier (BBB) using an in vitro model. Methods: The cell viability of the human brain endothelial cell line hCMEC/D3 after incubation with various concentrations of allicin was investigated using an MTT assay at 3 and 24 h. Additionally, reactive oxygen species (ROS) production of allicin-treated hCMEC/D3 cells was examined at 3 h. The concentrations of allicin that were not toxic to the cells, as determined by the MTT assay, and did not significantly increase ROS generation, were then used to investigate allicin's ability to traverse the in vitro BBB model for 3 h. High-performance liquid chromatography (HPLC) analysis was utilized to examine the allicin concentration capable of passing the in vitro BBB model. The cellular uptake experiments were subsequently performed to observe the uptake of allicin into hCMEC/D3 cells. The pkCSM online tool was used to predict the absorption, distribution, metabolism, excretion, and pharmacokinetic properties of allicin and S-allylmercaptoglutathione (GSSA). Results: The results from MTT assay indicated that the highest non-toxicity concentration of allicin on hCMEC/D3 cells was 5 µg/ml at 3 h and 2 µg/ml at 24 h. Allicin significantly enhanced ROS production of hCMEC/D3 cells at 10 µg/ml at 3 h. After applying the non-toxicity concentrations of allicin (0.5-5 µg/ml) to the in vitro BBB model for 3 h, allicin was not detectable in both apical and basolateral chambers in the presence of hCMEC/D3 cells. On the contrary, allicin was detected in both chambers in the absence of the cells. The results from cellular uptake experiments at 3 h revealed that hCMEC/D3 cells at 1 × 104 cells could uptake allicin at concentrations of 0.5, 1, and 2 µg/ml. Moreover, allicin uptake of hCMEC/D3 cells was proportional to the cell number, and the cells at 5 × 104 could completely uptake allicin at a concentration of 5 µg/ml within 0.5 h. The topological polar surface area (TPSA) predicting for allicin was determined to be 62.082 Å2, indicating its potential ability to cross the BBB. Additionally, the calculated logBB value surpassing 0.3 suggests that the compound may exhibit ease of penetration through the BBB. Conclusion: The present results suggested that allicin was rapidly taken up by hCMEC/D3 cells in vitro BBB model. The prediction results of allicin's distribution patterns suggested that the compound possesses the capability to enter the brain.


Assuntos
Barreira Hematoencefálica , Sobrevivência Celular , Dissulfetos , Células Endoteliais , Espécies Reativas de Oxigênio , Ácidos Sulfínicos , Ácidos Sulfínicos/farmacologia , Humanos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular , Cromatografia Líquida de Alta Pressão
4.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000066

RESUMO

Galectins are multifunctional effectors in cellular homeostasis and dysregulation. Oxidation of human galectin-1 (Gal-1) with its six sulfhydryls produces a disulfide-bridged oxidized form that lacks normal lectin activity yet gains new glycan-independent functionality. Nevertheless, the mechanistic details as to how Gal-1 oxidation occurs remain unclear. Here, we used 15N and 13C HSQC NMR spectroscopy to gain structural insight into the CuSO4-mediated path of Gal-1 oxidation and identified a minimum two-stage conversion process. During the first phase, disulfide bridges form slowly between C16-C88 and/or C42-C66 to produce a partially oxidized, conformationally flexible intermediate that retains the ability to bind lactose. Site-directed mutagenesis of C16 to S16 impedes the onset of this overall slow process. During the second phase, increased motional dynamics of the intermediate enable the relatively distant C2 and C130 residues to form the third and final disulfide bond, leading to an unfolded state and consequent dimer dissociation. This fully oxidized end state loses the ability to bind lactose, as shown by the hemagglutination assay. Consistent with this model, we observed that the Gal-1 C2S mutant maintains intermediate-state structural features with a free sulfhydryl group at C130. Incubation with dithiothreitol reduces all disulfide bonds and allows the lectin to revert to its native state. Thus, the sequential, non-random formation of three disulfide bridges in Gal-1 in an oxidative environment acts as a molecular switch for fundamental changes to its functionality. These data inspire detailed bioactivity analysis of the structurally defined oxidized intermediate in, e.g., acute and chronic inflammation.


Assuntos
Cisteína , Galectina 1 , Oxirredução , Galectina 1/metabolismo , Galectina 1/química , Galectina 1/genética , Humanos , Cisteína/metabolismo , Cisteína/química , Dissulfetos/metabolismo , Dissulfetos/química , Dobramento de Proteína , Desdobramento de Proteína , Modelos Moleculares , Lactose/metabolismo , Lactose/química , Mutagênese Sítio-Dirigida
5.
Nat Commun ; 15(1): 5939, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009599

RESUMO

The precise regulation of protein function is essential in biological systems and a key goal in chemical biology and protein engineering. Here, we describe a straightforward method to engineer functional control into the isopeptide bond-forming SpyTag/SpyCatcher protein ligation system. First, we perform a cysteine scan of the structured region of SpyCatcher. Except for two known reactive and catalytic residues, none of these mutations abolish reactivity. In a second screening step, we modify the cysteines with disulfide bond-forming small molecules. Here we identify 8 positions at which modifications strongly inhibit reactivity. This inhibition can be reversed by reducing agents. We call such a reversibly inhibitable SpyCatcher "SpyLock". Using "BiLockCatcher", a genetic fusion of wild-type SpyCatcher and SpyLock, and SpyTagged antibody fragments, we generate bispecific antibodies in a single, scalable format, facilitating the screening of a large number of antibody combinations. We demonstrate this approach by screening anti-PD-1/anti-PD-L1 bispecific antibodies using a cellular reporter assay.


Assuntos
Anticorpos Biespecíficos , Cisteína , Engenharia de Proteínas , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/química , Humanos , Engenharia de Proteínas/métodos , Cisteína/química , Cisteína/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Células HEK293 , Dissulfetos/química , Animais
6.
Nat Commun ; 15(1): 5535, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951545

RESUMO

The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16INK4a leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils. The stable amyloid structures disassemble when the disulfide bond is reduced. p16INK4a is frequently mutated in cancers and is considered highly vulnerable to single-point mutations. We find that multiple cancer-related mutations show increased amyloid formation propensity whereas mutations stabilizing the fold prevent transition into amyloid. The complex transition into amyloids and their structural stability is therefore strictly governed by redox reactions and a single regulatory disulfide bond.


Assuntos
Amiloide , Inibidor p16 de Quinase Dependente de Ciclina , Cisteína , Oxirredução , Amiloide/metabolismo , Amiloide/química , Humanos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Cisteína/metabolismo , Cisteína/química , Dissulfetos/metabolismo , Dissulfetos/química , Compostos de Sulfidrila/metabolismo , Compostos de Sulfidrila/química , Mutação , Polimerização
7.
Nat Commun ; 15(1): 6124, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033137

RESUMO

Insulin icodec is a once-weekly insulin analogue that has a long half-life of approximately 7 days, making it suitable for once weekly dosing. The Insulin icodec molecule was developed based on the hypothesis that lowering insulin receptor affinity and introducing a strong albumin-binding moiety would result in a long insulin half-life, provided that non-receptor-mediated clearance is diminished. Here, we report an insulin clearance mechanism, resulting in the splitting of insulin molecules into its A-chain and B-chain by a thiol-disulphide exchange reaction. Even though the substitutions in insulin icodec significantly stabilise insulin against such degradation, some free B-chain is observed in plasma samples from minipigs and people with type 2 diabetes. In summary, we identify thiol-disulphide exchange reactions to be an important insulin clearance mechanism and find that stabilising insulin icodec towards this reaction significantly contributes to its long pharmacokinetic/pharmacodynamic profile.


Assuntos
Diabetes Mellitus Tipo 2 , Dissulfetos , Insulina , Porco Miniatura , Animais , Suínos , Dissulfetos/química , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangue , Insulina/administração & dosagem , Insulina/metabolismo , Insulina/química , Insulina/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/química , Meia-Vida , Receptor de Insulina/metabolismo , Masculino , Compostos de Sulfidrila/química
8.
Methods Mol Biol ; 2839: 249-259, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008259

RESUMO

Thiol-disulfide interconversions are pivotal in the intricate chemistry of biological systems. They play a vital role in governing cellular redox potential and shielding against oxidative harm. These interconversions can also act as molecular switches within an expanding array of redox-regulated proteins, facilitating dynamic and responsive processes. Furthermore, metal-binding proteins often use thiols for coordination. Reverse thiol trapping is a valuable analytical tool to study the redox state of cysteines in biological systems. By selectively capturing and stabilizing free thiol species with an alkylating agent, reverse thiol trapping allows for their subsequent identification and quantification. Various methods can be employed to analyze the trapped thiol adducts, including electrophoresis-based methods, mass spectrometry, nuclear magnetic resonance spectroscopy, and chromatographic techniques. In this chapter, we will focus on describing a simple and sensitive method to sequentially block thiols in their cellular state with a cell-permeant agent (iodoacetamide), and following reduction and denaturation of the samples, trap the native disulfides with a second blocker that shifts the apparent molecular weight of the protein. The oxidation status of proteins for which suitable antibodies are available can then be analyzed by immunoblotting. We present examples of mitochondrial proteins that use cysteine thiols to coordinate metal factors such as iron-sulfur clusters, zinc, and copper.


Assuntos
Proteínas Mitocondriais , Oxirredução , Compostos de Sulfidrila , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/química , Humanos , Iodoacetamida/química , Dissulfetos/química , Dissulfetos/metabolismo , Metais/química , Metais/metabolismo , Cisteína/química , Cisteína/metabolismo
9.
Langmuir ; 40(28): 14346-14354, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38953474

RESUMO

The issue of bacterial infectious diseases remains a significant concern worldwide, particularly due to the misuse of antibiotics, which has caused the emergence of antibiotic-resistant strains. Fortunately, the rapid development of nanomaterials has propelled significant progress in antimicrobial therapy, offering promising solutions. Among them, the utilization of nanoenzyme-based chemodynamic therapy (CDT) has become a highly hopeful approach to combating bacterial infectious diseases. Nevertheless, the application of CDT appears to be facing certain constraints for its low efficiency in the Fenton reaction at the infected site. In this study, we have successfully synthesized a versatile nanozyme, which was a composite of molybdenum sulfide (MoS2) and iron sulfide (FeS2), through the hydrothermal method. The results showed that iron/molybdenum sulfide nanozymes (Fe/Mo SNZs) with desirable peroxidase (POD) mimic activity can generate cytotoxic reactive oxygen species (ROS) by successfully triggering the Fenton reaction. The presence of MoS2 significantly accelerates the conversion of Fe2+/Fe3+ through a cocatalytic reaction that involves the participation of redox pairs of Mo4+/Mo6+, thereby enhancing the efficiency of CDT. Additionally, based on the excellent photothermal performance of Fe/Mo SNZs, a near-infrared (NIR) laser was used to induce localized temperature elevation for photothermal therapy (PTT) and enhance the POD-like nanoenzymatic activity. Notably, both in vitro and in vivo results demonstrated that Fe/Mo SNZs with good broad-spectrum antibacterial properties can help eradicate Gram-negative bacteria like Escherichia coli and Gram-positive bacteria like Staphylococcus aureus. The most exciting thing is that the synergistic PTT/CDT exhibited astonishing antibacterial ability and can achieve complete elimination of bacteria, which promoted wound healing after infection. Overall, this study presents a synergistic PTT/CDT strategy to address antibiotic resistance, providing avenues and directions for enhancing the efficacy of wound healing treatments and offering promising prospects for further clinical use in the near future.


Assuntos
Antibacterianos , Dissulfetos , Ferro , Molibdênio , Sulfetos , Cicatrização , Molibdênio/química , Molibdênio/farmacologia , Cicatrização/efeitos dos fármacos , Sulfetos/química , Sulfetos/farmacologia , Animais , Dissulfetos/química , Dissulfetos/farmacologia , Ferro/química , Ferro/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Catálise , Staphylococcus aureus/efeitos dos fármacos , Camundongos , Escherichia coli/efeitos dos fármacos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Nanoestruturas/química , Fototerapia , Testes de Sensibilidade Microbiana , Terapia Fototérmica , Compostos Ferrosos
10.
J Agric Food Chem ; 72(28): 15971-15984, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38959404

RESUMO

Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1'-hydroxyl and 3'-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by SN1 and/or SN2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.


Assuntos
Ativação Metabólica , Derivados de Alilbenzenos , Sistema Enzimático do Citocromo P-450 , RNA , Sulfotransferases , Espectrometria de Massas em Tandem , Animais , Camundongos , Sulfotransferases/metabolismo , Sulfotransferases/genética , Sulfotransferases/química , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/química , Derivados de Alilbenzenos/química , Derivados de Alilbenzenos/metabolismo , RNA/metabolismo , RNA/química , Masculino , Hepatócitos/metabolismo , Dioxolanos/metabolismo , Dioxolanos/química , Dioxolanos/toxicidade , Fígado/metabolismo , Fígado/enzimologia , Dissulfetos/química , Dissulfetos/metabolismo , Myristica/química , Myristica/metabolismo
11.
Environ Sci Pollut Res Int ; 31(33): 45588-45601, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967847

RESUMO

The performance of catalytic ability of MFe2O4/MoS2 in the ozonation process was investigated in this work. The synthesized MnFe2O4/MoS2 was optimize prepared and then characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photo-electron spectroscopy, and magnetic saturation strength. The results showed that when Cphenol = 200 mg/L, initial pH = 9.0, Q = 0.10 L/min, and CMnFe2O4/MoS2 = 0.10 g/L, MnFe2O4/MoS2 addition improved the degradation efficiency of phenol by 20.0%. The effects of pH, catalyst dosage, and inorganic ions on the phenol removal by the MnFe2O4/MoS2 catalytic ozonation were investigated. Five cycle experiments proved that MnFe2O4/MoS2 had good recyclability and stability. MnFe2O4/MoS2 also showed good catalytic performance in the treatment of coal chemical wastewater pesticide wastewater. The MnFe2O4 doped with MoS2 could provide abundant surface active sites for ozone and promote the stable cycle of Mn2+/Mn3+and Fe2+/Fe3+, thus generating large amounts of •OH and improving the degradation of phenol by ozonation. The MnFe2O4/MoS2/ozonation treatment system provides a technical reference and theoretical basis for industrial wastewater treatment.


Assuntos
Ozônio , Águas Residuárias , Águas Residuárias/química , Ozônio/química , Catálise , Compostos Férricos/química , Compostos de Manganês/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Purificação da Água/métodos , Fenóis/química , Molibdênio/química , Dissulfetos/química
12.
J Nanobiotechnology ; 22(1): 337, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886712

RESUMO

BACKGROUND: Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear. METHODS: In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months. RESULTS: These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group. CONCLUSION: We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.


Assuntos
Celulose , Dissulfetos , Molibdênio , Regeneração Nervosa , Células de Schwann , Alicerces Teciduais , Regeneração Nervosa/efeitos dos fármacos , Animais , Ratos , Alicerces Teciduais/química , Dissulfetos/química , Dissulfetos/farmacologia , Células de Schwann/efeitos dos fármacos , Molibdênio/química , Molibdênio/farmacologia , Celulose/química , Celulose/farmacologia , Celulose/análogos & derivados , Ratos Sprague-Dawley , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Proliferação de Células/efeitos dos fármacos , Engenharia Tecidual/métodos , Masculino , Traumatismos dos Nervos Periféricos , Estereoisomerismo
13.
ACS Nano ; 18(26): 16853-16866, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38896491

RESUMO

The precise modulation of electrical activity in specific neuronal populations is paramount for rectifying abnormal neurological functions and is a critical element in the therapeutic arsenal for neurological disorders. However, achieving a balance between minimal invasiveness and robust neuroprotection poses a considerable challenge. Herein, we present a nanoneuromodulation strategy integrating neuroprotective features to effectively address epilepsy with minimal invasiveness and enable wireless functionality. Strategically engineered nanotransducer, adorned with platinum (Pt) decoration with titanium disulfide (TiS2) (TiS2/Pt), enables precise modulation of neuronal electrical activity in vitro and in vivo, ensuring exceptional temporal fidelity under millisecond-precision near-infrared (NIR) light pulses irradiation. Concurrently, TiS2/Pt showcase a pronounced enhancement in enzyme-mimicking activity, offering a robust defense against oxidative neurological injury in vitro. Nanotransducer-enabled wireless neuromodulation with biocatalytic neuroprotective capacity is highly effective in alleviating epileptic high-frequency neural activity and diminishing oxidative stress levels, thereby restoring redox equilibrium. This integrated therapeutic approach reduces the severity of epilepsy, demonstrating minimal invasiveness and obviating the requirements for genetic manipulation and optical fiber implantation, while providing an alternative avenue for neurological disorder treatment.


Assuntos
Epilepsia , Epilepsia/terapia , Animais , Titânio/química , Titânio/farmacologia , Platina/química , Platina/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Neuroproteção/efeitos dos fármacos , Camundongos , Dissulfetos/química , Dissulfetos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Humanos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Raios Infravermelhos , Ratos
14.
Biomater Adv ; 162: 213920, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38901063

RESUMO

Chronic refractory wounds caused by multidrug-resistant (MDR) bacterial and biofilm infections are a substantial threat to human health, which presents a persistent challenge in managing clinical wound care. We here synthesized a composite nanosheet AIPH/AMP/MoS2, which can potentially be used for combined therapy because of the photothermal effect induced by MoS2, its ability to deliver antimicrobial peptides, and its ability to generate alkyl free radicals independent of oxygen. The synthesized nanosheets exhibited 61 % near-infrared (NIR) photothermal conversion efficiency, marked photothermal stability and free radical generating ability. The minimal inhibitory concentrations (MICs) of the composite nanosheets against MDR Escherichia coli (MDR E. coli) and MDR Staphylococcus aureus (MDR S. aureus) were approximately 38 µg/mL and 30 µg/mL, respectively. The composite nanosheets (150 µg/mL) effectively ablated >85 % of the bacterial biofilm under 808-nm NIR irradiation for 6 min. In the wound model experiment, approximately 90 % of the wound healed after the 4-day treatment with the composite nanosheets. The hemolysis experiment, mouse embryonic fibroblast (MEFs) cytotoxicity experiment, and mouse wound healing experiment all unveiled the excellent biocompatibility of the composite nanosheets. According to the transcriptome analysis, the composite nanosheets primarily exerted a synergistic therapeutic effect by disrupting the cellular membrane function of S. aureus and inhibiting quorum sensing mediated by the two-component system. Thus, the synthesized composite nanosheets exhibit remarkable antibacterial and biofilm ablation properties and therefore can be used to improve wound healing in chronic biofilm infections.


Assuntos
Biofilmes , Dissulfetos , Escherichia coli , Molibdênio , Staphylococcus aureus , Cicatrização , Biofilmes/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Camundongos , Dissulfetos/química , Dissulfetos/farmacologia , Molibdênio/química , Molibdênio/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Radicais Livres/química , Radicais Livres/metabolismo , Nanoestruturas/química , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Temperatura Alta , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química
15.
J Colloid Interface Sci ; 672: 236-243, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38838631

RESUMO

This study reports the development of a photocatalytic electrochemical aptasensor for the purpose of detecting chloramphenicol (CAP) antibiotic residues in water by utilizing SYBR Green I (SG) and chemically exfoliated MoS2 (ce-MoS2) as synergistically signal-amplification platforms. The Au nanoparticles (AuNPs) were electrodeposited onto the surface of an indium tin oxide (ITO) electrode. After that, the thiolate-modified cDNA, also known as capture DNA, was combined with the aptamer. Subsequently, photosensitized SG molecules and ce-MoS2 nanomaterial were inserted into the groove of the resultant double-stranded DNA (dsDNA). The activation of the photocatalytic process upon exposure to light resulted in the generation of singlet oxygen. The singlet oxygen effectively split the dsDNA, resulting in significant enhancement in the current of [Fe(CN)6]3-/4-. When the CAP was present, both SG molecules and ce-MoS2 broke away from the dsDNA, which turned off the photosensitization response, leading to significant reduction in the current of [Fe(CN)6]3-/4-. Under the optimal conditions, the aptasensor exhibited a linear relationship between the current of [Fe(CN)6]3-/4- with logarithmic concentrations of CAP from 20 to 1000 nM, with a detection of limit (3σ) of 3.391 nM. The aptasensor also demonstrated good selectivity towards CAP in the presence of interfering antibiotics, such as tetracycline, streptomycin, levofloxacin, ciprofloxacin, and sulfadimethoxine. Additionally, the results obtained from the analysis of natural water samples using the proposed aptasensor were consistent with the findings acquired through the use of a liquid chromatograph-mass spectrometer. Therefore, with its simplicity and high selectivity, this aptasensor can potentially detect alternative antibiotics in environmental water samples by replacing the aptamers based on photosensitization.


Assuntos
Aptâmeros de Nucleotídeos , Benzotiazóis , Técnicas Biossensoriais , Cloranfenicol , Diaminas , Dissulfetos , Técnicas Eletroquímicas , Molibdênio , Compostos Orgânicos , Quinolinas , Cloranfenicol/análise , Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Molibdênio/química , Diaminas/química , Dissulfetos/química , Benzotiazóis/química , Quinolinas/química , Compostos Orgânicos/química , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Ouro/química , Fármacos Fotossensibilizantes/química , Antibacterianos/análise , Limite de Detecção , Poluentes Químicos da Água/análise , Processos Fotoquímicos , Tamanho da Partícula
16.
Int J Biol Macromol ; 273(Pt 2): 133156, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878932

RESUMO

The environmental benefits of utilizing protease as a biocatalyst for wool shrink-resist finishing have been widely recognized. However, the efficacy of individual protease treatment is unsatisfactory due to its incapability towards the outermost cuticle layer of wool fibers that contains hydrophobic fatty acids. In order to weaken the structural integrity of the highly cross-linked scales and promote the enzymatic anti-felting, sodium sulfite and tris (2-carboxyethyl) phosphine hydrochloride (TCEP) were employed in combination with papain, respectively, aiming at obtaining a low shrinkage without unacceptable fiber damages. Based on the synergistic effect of papain and TCEP, the edges of wool scales were slightly destroyed by the reduction of disulfide bonds, accompanied by enzymatic hydrolysis of the keratin component. Through the controlled reduction and hydrolysis of wool scales, satisfactory anti-felting result was achieved without causing severe damage to the fiber interiors. In the presence of 0.25 g/L TCEP and 25 U/mL papain, the area shrinkage of wool fabric decreased to approximately 6 %, with a low strength loss of less than 8 %. Meanwhile, the dyeing behavior of the wool fabric under low-temperature conditions was dramatically improved, leading to decreased energy consumption during production. The present work provides an alternative for eco-friendly finishing of wool fabrics, which can be applied commercially.


Assuntos
Dissulfetos , Papaína , , Papaína/química , Animais , Lã/química , Dissulfetos/química , Substâncias Redutoras/química , Sulfitos/química , Sulfitos/farmacologia , Fosfinas/química , Fibra de Lã , Hidrólise , Têxteis
17.
Int J Biol Macromol ; 273(Pt 2): 133119, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38880452

RESUMO

Ethyl cellulose (EC)-based composite sponges were developed for oil spillage treatment. The EC sponge surface was decorated with helical carbon nanotubes (HCNTs) and molybdenum disulfide (MoS2) (1 phr) using the inside-out sugar templating method. The inside surface of a sugar cube was coated with HCNTs and MoS2. After filling the sugar cube pores with EC and the subsequent sugar leaching, the decorating materials presented on the sponge surface. The EC/HCNT/MoS2 sponge had a high level of oil removal based on its adsorption capacity (41.68 g/g), cycled adsorption (∼75-79 %), separation flux efficiency (∼85-95 %), and efficiency in oil/water emulsion separation (92-94 %). The sponge maintained adsorption capacity in acidic, basic, and salty conditions, adsorbed oil under water, and functioned as an oil/water separator in a continuous pump-assisted system. The compressive stress and Young's modulus of the EC sponge increased following its decoration using HCNTs and MoS2. The composite sponge was robust based on cycled compression and was thermally stable up to ∼120 οC. Based on the eco-friendliness of EC, the low loading of HCNTs and MoS2, and sponge versatility, the developed EC/HCNT/MoS2 sponge should be good candidate for use in sustainable oil adsorption and separation applications.


Assuntos
Celulose , Dissulfetos , Molibdênio , Nanotubos de Carbono , Celulose/química , Celulose/análogos & derivados , Dissulfetos/química , Nanotubos de Carbono/química , Adsorção , Molibdênio/química , Água/química , Óleos/química , Purificação da Água/métodos
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124675, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-38906057

RESUMO

Molybdenum disulfide (MoS2) quantum dots (QDs) based therapeutic approaches hold great promise for biomedical applications, necessitating a thorough evaluation of their potential effects on biological systems. In this study, we systematically investigated the impact of MoS2 QDs coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)-2000](DPSE-PEG) linked with (3-carboxypropyl)triphenyl-phosphonium-bromide (TPP) on molecular structures of hepatic tissue lipids and proteins through a multifaceted analysis. The DSPE-PEG-TPP-MoS2 QDs were prepared and administered to the mice daily for 7 weeks. Liver tissues were subjected to a comprehensive examination using various techniques, including Fourier-transform infrared (FTIR) spectroscopy, UV-vis spectroscopy, and liver function tests. FTIR revealed subtle changes in the lipid composition of liver tissues, indicating potential modifications in the cell membrane structure. Also, the (CH stretching and amides I and II regions) analysis unveiled tiny alterations in lipid chain length and fluidity without changes in the protein structures, suggesting a minor influence of DSPE-PEG-TPP-MoS2 QDs on the liver's cellular membrane and no effect on the protein structures. Further scrutiny using UV-vis spectroscopy demonstrated that DSPE-PEG-TPP-MoS2 QDs had no discernible impact on the absorbance intensities of aromatic amino acids and the Soret band. This observation implies that the treatment with SPE-PEG-TPP-MoS2 QDs did not induce significant alterations in helical conformation or the microenvironment surrounding prosthetic groups in liver tissues. The liver function tests, including ALP, ALT, AST, and BIL levels, revealed no statistically significant changes in these key biomarkers despite minor fluctuations in their values, indicating a lack of significant liver dysfunction. This study provides a detailed understanding of the effects of DSPE-PEG-TPP-MoS2 QDs on hepatic lipids and proteins, offering valuable insights into the biocompatibility and limited impact on the molecular and functional aspects of the liver tissue. These findings could be essential for the application of MoS2 QDs-based therapies.


Assuntos
Dissulfetos , Fígado , Molibdênio , Fosfatidiletanolaminas , Polietilenoglicóis , Pontos Quânticos , Pontos Quânticos/química , Molibdênio/química , Animais , Dissulfetos/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Polietilenoglicóis/química , Fosfatidiletanolaminas/química , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier , Lipídeos/química , Masculino , Proteínas/química
19.
Biosens Bioelectron ; 261: 116502, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38896980

RESUMO

Oxidative stress is widely recognized as a pivotal factor contributing to numerous Central Nervous System (CNS) ailments. The concentrations of hydrogen peroxide (H2O2) and phosphorylated proteins within the human body serve as crucial indicators of oxidative stress. As such, the real-time monitoring of H2O2 and phosphorylated proteins in sweat is vital for the early identification, diagnosis, and management of diseases linked to oxidative stress. In this context, we present a novel microfluidic wearable electrochemical sensor by modifying the electrode with Prussian blue (PB) and loading sulfur-rich vacancy-containing molybdenum disulfide (MoS2-X) onto Multi-walled carbon nanotube (CNTs) to form coaxially layered CNTs/MoS2-X, which was then synthesized with highly dispersed titanium dioxide nanoparticles (TiO2) to synthesize CNTs/MoS2-X/TiO2 composites for the detection of human sweat H2O2 and phosphorylated proteins, respectively. This structure, with its sulfur vacancies and coaxial layering, significantly improved sensitivity of electrochemical sensors, allowing it to detect H2O2 in a range of 0.01-1 mM with a detection limit of 4.80 µM, and phosphoproteins in a range of 0.01-1 mg/mL with a threshold of 0.917 µg/mL. Furthermore, the miniature sensor demonstrates outstanding performance in detecting analytes in both simulated and real sweat. Comprehensive biosafety assessments have validated the compatibility of the electrode material, underscoring the potential of sensor as a reliable and non-invasive method for tracking biomarkers linked to CNS disorders. This microfluidic wearable electrochemical biosensor with high performance and biosafety features shows great promise for the development of cutting-edge wearable technology devices for tracking CNS disease indicators.


Assuntos
Biomarcadores , Técnicas Biossensoriais , Técnicas Eletroquímicas , Peróxido de Hidrogênio , Nanotubos de Carbono , Estresse Oxidativo , Suor , Titânio , Dispositivos Eletrônicos Vestíveis , Humanos , Técnicas Biossensoriais/instrumentação , Biomarcadores/análise , Nanotubos de Carbono/química , Suor/química , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Titânio/química , Molibdênio/química , Ferrocianetos/química , Dissulfetos/química , Limite de Detecção , Desenho de Equipamento
20.
Acta Med Okayama ; 78(3): 259-270, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38902214

RESUMO

The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients' sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol-disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol-disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol-disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol-disulfide homeostasis in multiple sclerosis patients.


Assuntos
Disfunção Cognitiva , Fadiga , Lipídeos , Esclerose Múltipla , Estresse Oxidativo , Transtornos do Sono-Vigília , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/sangue , Adulto , Esclerose Múltipla/complicações , Esclerose Múltipla/sangue , Fadiga/etiologia , Fadiga/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Lipídeos/sangue , Homeostase , Albumina Sérica Humana/análise , Dissulfetos/sangue , Compostos de Sulfidrila/sangue , Biomarcadores
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