Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 123
Filtrar
1.
Food Chem ; 463(Pt 3): 141441, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39340904

RESUMEN

Exploring materials with the dual functionality of detecting and removing tetracycline (TC) residues is crucial because of the environmental and health risks posed by antibiotic overuse. This study introduces a dual-emissive luminescent probe, CDs@ZSM-5:Eu3+, created through a solvent-free method combined with subsequent Eu3+ion exchange. The nanocomposite's blue emission, originating from carbon dots (CDs), is quenched by TC via an internal filtering effect, while an antenna effect triggers a strong red fluorescence of a TC-Eu3+chelate. The ratiometric fluorescence changes in CDs@ZSM-5:Eu3+ endow a self-calibrated sensing mechanism for TC, offering a low detection limit of 5.04 nM and a broad detection range of 0.01-50 µM. Demonstrated in real milk samples, the probe exhibits high selectivity and accuracy in detecting TC. The nanocomposite also displayed an impressive TC removal capacity of 238.1 mg g-1 in water, ascribing to the enrichment and electrostatic attraction effects of ZSM-5 toward TC molecules. This research offers a facile strategy for constructing multifunctional zeolite-based hybrids for simultaneous TC detection and removal from aqueous solutions.

2.
Org Biomol Chem ; 22(37): 7549-7559, 2024 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-39192765

RESUMEN

Mass spectrometry, coupled with innovative crosslinking techniques to decode protein conformations and interactions through uninterrupted signal connections, has undergone remarkable progress in recent years. It is crucial to develop selective crosslinking reagents that minimally disrupt protein structure and dynamics, providing insights into protein network regulation and biological functions. Compared to traditional crosslinkers, new bifunctional chemical crosslinkers exhibit high selectivity and specificity in connecting proximal amino acid residues, resulting in stable molecular crosslinked products. The conjugation with specific amino acid residues like lysine, cysteine, arginine and tyrosine expands the XL-MS toolbox, enabling more precise modeling of target substrates and leading to improved data quality and reliability. Another emerging crosslinking method utilizes unnatural amino acids (UAAs) derived from proximity-enabled reactivity with specific amino acids or sulfur-fluoride exchange (SuFEx) reactions with nucleophilic residues. These UAAs are genetically encoded into proteins for the formation of specific covalent bonds. This technique combines the benefits of genetic encoding for live cell compatibility with chemical crosslinking, providing a valuable method for capturing transient and weak protein-protein interactions (PPIs) for mapping PPI coordinates and improving the pharmacological properties of proteins. With continued advancements in technology and applications, crosslinking mass spectrometry is poised to play an increasingly significant role in guiding our understanding of protein dynamics and function in the future.


Asunto(s)
Reactivos de Enlaces Cruzados , Proteínas , Reactivos de Enlaces Cruzados/química , Proteínas/química , Proteínas/metabolismo , Humanos , Espectrometría de Masas , Aminoácidos/química , Aminoácidos/metabolismo
3.
Polymers (Basel) ; 16(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39125140

RESUMEN

The development of more recyclable materials is a key requirement for a transition towards a more circular economy. Thanks to exchange reactions, vitrimer, an attractive alternative for recyclable materials, is an innovative class of polymers that is able to change its topology without decreasing its connectivity. In this work, a bisphenol compound (VP) was prepared from saturated cardanol, i.e., 3-pentadecylphenol and vanillyl alcohol. Then, VP was epoxidized to obtain epoxide (VPGE). Finally, VPGE and citric acid (CA) were polymerized in the presence of catalyst TBD to prepare a fully bio-based vitrimer based on transesterification. The results from differential scanning calorimetry (DSC) showed that the VPGE/CA system could be crosslinked at around 163 °C. The cardanol-derived vitrimers had good network rearrangement properties. Meanwhile, because of the dynamic structural elements in the network, the material was endowed with excellent self-healing, welding, and recyclability.

4.
Phytochem Anal ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38957046

RESUMEN

INTRODUCTION: Sophora flavescens Aiton (Fabaceae), a ubiquitous plant species in Asia, contains a wide range of pharmacologically active compounds, such as flavonoids, with potential anti-Alzheimer's disease (anti-AD) effects. OBJECTIVES: The objective of the study is to develop a quaternity method for the screening, isolation, extraction optimization, and activity evaluation of acetylcholinesterase (AChE)-inhibiting compounds from S. flavescens to realize high-throughput screening of active substances in traditional Chinese medicine and to provide experimental data for the development of anti-AD drugs. METHODS: With AChE as the target molecule, affinity ultrafiltration and liquid chromatography-mass spectrometry were applied to screen for potential inhibitors of the enzyme in S. flavescens. Orthogonal array experiments combined with the multi-objective Non-Dominated Sorting Genetic Algorithm III was used for the first time to optimize the process for extracting the active substances. Enzyme inhibition kinetics and molecular docking studies were performed to verify the potential anti-AD effects of the active compounds. RESULTS: Five AChE-inhibiting compounds were identified: kushenol I, kurarinone, sophoraflavanone G, isokurarinone, and kushenol E. These were successfully separated at purities of 72.88%, 98.55%, 96.86%, 96.74%, and 95.84%, respectively, using the n-hexane/ethyl acetate/methanol/water (4.0/5.0/4.0/5.0, v/v/v/v), n-hexane/ethyl acetate/methanol/water (5.0/5.0/6.0/4.0, v/v/v/v), and n-hexane/ethyl acetate/methanol/water (4.9/5.1/5.7/4.3, v/v/v/v) mobile phase systems. Enzyme inhibition kinetics revealed that kushenol E had the best inhibitory effect. CONCLUSION: This study elucidates the mechanism of action of five active AChE inhibitors in S. flavescens and provides a theoretical basis for the screening and development of anti-AD and other therapeutic drugs.

5.
ACS Sens ; 9(7): 3641-3651, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-38967239

RESUMEN

Limited by insufficient active sites and restricted mechanical strength, designing reliable and wearable gas sensors with high activity and ductility remains a challenge for detecting hazardous gases. In this work, a thermally induced and solvent-assisted oxyanion etching strategy was implemented for selective pore opening in a rigid microporous Cu-based metal-organic framework (referred to as CuM). A conductive CuM/MXene aerogel was then self-assembled through cooperative hydrogen bonding interactions between the carbonyl oxygen atom in PVP grafted on the surface of defect-rich Cu-BTC and the surface functional hydroxyl group on MXene. A flexible NO2 sensing performance using the CuM/MXene aerogel hybridized sodium alginate hydrogel is finally achieved, demonstrating extraordinary sensitivity (S = 52.47 toward 50 ppm of NO2), good selectivity, and rapid response/recovery time (0.9/4.5 s) at room temperature. Compared with commercial sensors, the relative error is less than 7.7%, thereby exhibiting significant potential for application in monitoring toxic and harmful gases. This work not only provides insights for guiding rational synthesis of ideal structure models from MOF composites but also inspires the development of high-performance flexible gas sensors for potential multiscenario applications.


Asunto(s)
Enlace de Hidrógeno , Estructuras Metalorgánicas , Temperatura , Estructuras Metalorgánicas/química , Geles/química , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/química , Cobre/química , Gases/química , Gases/análisis , Alginatos/química
6.
Molecules ; 29(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38893462

RESUMEN

Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from Taxus or chemical synthesis using 10-deacetylbaccatin III (10-DAB) as substrate. However, these preparation approaches exhibit serious limitations, including the low content of baccatin III in Taxus and the complicated steps of chemical synthesis. Heterologous expression of 10-deacetylbaccatin III-10-O-acetyltransferase (TcDBAT) in microbial strains for biotransformation of 10-DAB is a promising alternative strategy for baccatin III production. Here, the promotion effects of glycerol supply and slightly acidic conditions with a low-temperature on the catalysis of recombinant TcDBAT strain were clarified using 10-DAB as substrate. Taxus needles is renewable and the content of 10-DAB is relatively high, it can be used as an effective source of the catalytic substrate 10-DAB. Baccatin III was synthesized by integrating the extraction of 10-DAB from renewable Taxus needles and in situ whole-cell catalysis in this study. 40 g/L needles were converted into 20.66 mg/L baccatin III by optimizing and establishing a whole-cell catalytic bioprocess. The method used in this study can shorten the production process of Taxus extraction for baccatin III synthesis and provide a reliable strategy for the efficient production of baccatin III by recombinant strains and the improvement of resource utilization rate of Taxus needles.


Asunto(s)
Biotransformación , Taxoides , Taxus , Taxus/metabolismo , Taxus/química , Taxoides/metabolismo , Alcaloides/biosíntesis , Alcaloides/metabolismo , Alcaloides/química , Hojas de la Planta/metabolismo , Hojas de la Planta/química , Acetiltransferasas/metabolismo , Acetiltransferasas/genética
7.
Chempluschem ; : e202400235, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760894

RESUMEN

Electrodeposition of abundant metals to fabricate efficient and durable electrodes indicate a viable role in advancing renewable electrochemical energy tools. Herein, we deposit Co9S8-Ag-Ni3S2@NF on nickel foam (NF) to produce Co9S8-Ag-Ni3S2@NF as a exceedingly proficient electrode for oxygen evolution reaction (OER). The electrochemical investigation verifies that the Co9S8-Ag-Ni3S2@NF electrode reveals better electrocatalytic activity to OER because of its nanoflowers' open-pore morphology, reduced overpotential (η10=125 mV), smaller charge transfer resistance, long-term stability, and a synergistic effect between various components, which allows the reactants to be more easily absorbed and subsequently converted into gaseous products during the water electrolysis route. Density functional theory (DFT) calculation as well reveals the introduction of Ag (222) surface into the Co9S8 (440)-Ni3S2 (120) structure increases the electronic density of states (DOS) per unit cell of a system and increases the electrocatalytic activity of OER by considerably lowering the energy barriers of its intermediates. This study provides the innovation of employing trimetallic nanomaterials immobilized on a conductive, continuous porous three-dimensional network formed on a nickel foam (NF) substrate as a highly proficient catalyst for OER.

8.
ACS Appl Mater Interfaces ; 16(19): 25090-25100, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38709646

RESUMEN

The selective electrocatalytic reduction of nitrobenzene (NB) to aniline demands a desirable cathodic catalyst to overcome the challenges of the competing hydrogen evolution reaction (HER), a higher overpotential, and a lower selectivity. Here, we deposit Co-doped 1T MoS2 on Ti mesh by the solvothermal method with different doping percentages of Co as x % Co-MoS2 (where x = 3, 5, 8, 10, and 12%). Because of the lowest overpotential, lower charge-transfer resistance, strong suppression of the competing HER, and higher electrochemical surface area, 8% Co-MoS2 achieves 94% selectivity of aniline with 54% faradaic efficiency. The reduction process follows first-order dynamics with a reaction coefficient of 0.5 h-1. Besides, 8% Co-MoS2 is highly stable and retains 81% selectivity even after 8 cycles. Mechanistic studies showed that the selective and exothermic adsorption of the nitro group at x % Co-MoS2 leads to a higher rate of NB reduction and higher selectivity of aniline. The aniline product is successfully removed from the solution by polymerization at FTO. This study signifies the impact of doping metal atoms in tuning the electronic arrangement of 1T-MoS2 for the facilitation of organic transformations.

9.
Fitoterapia ; 175: 105856, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38354820

RESUMEN

Poria cocos (Schw.) Wolf (P. cocos) has been widely used as medical plant in East Asia with remarkable anti-Alzheimer's disease (anti-AD) activity. However, the underlying mechanisms are still confused. In this study, based on the ß-Amyloid deposition hypothesis of AD, an integrated analysis was conducted to screen and separation 5-lipoxygenase (5-LOX) inhibitors from triterpenoids of P. cocos and investigate the anti-AD mechanisms, containing bioaffinity ultrafiltration UPLC-Q-Exactive, molecular docking, and multiple complex networks. Five triterpenoids were identified as potential 5-LOX inhibitors, including Tumulosic acid, Polyporenic acid C, 3-Epi-dehydrotumulosic acid, Pachymic acid and Dehydrotrametenolic acid. Five potential 5-LOX inhibitors were screened by ultrafiltration affinity assay in P. cocos. The molecular docking simulation results are consistent with the ultrafiltration experimental results, which further verifies the accuracy of the experiment. The commercial 5-LOX inhibitor that Zileuton was used as a positive control to evaluate the inhibitory effect of active ingredients on 5-LOX. Subsequently, the established separation method allowed the five active ingredients (Pachymic acid, 3-Epi-dehydrotumulosic acid, Dehydrotrametenolic acid, Tumulosic acid and Polyporenic acid C) with high purity to be isolated. Targeting network pharmacology analysis showed that five active ingredients correspond to a total of 286 targets. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis found that target cells were mainly enriched in Pathways in cancer, Lipid and atherosclerosis. Our results indicate that P. cocos extract has the potential to be used in the prevention and treatment of neurodegenerative diseases. This will help elucidate the mechanisms of action of various medicinal plants at the molecular level and provide more opportunities for the discovery and development of new potential treatments from health food resources.


Asunto(s)
Inhibidores de la Lipooxigenasa , Simulación del Acoplamiento Molecular , Triterpenos , Wolfiporia , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/química , Inhibidores de la Lipooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/aislamiento & purificación , Wolfiporia/química , Estructura Molecular , Ultrafiltración , Araquidonato 5-Lipooxigenasa/metabolismo , Cromatografía Líquida de Alta Presión , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Plantas Medicinales/química , Farmacología en Red
10.
Geroscience ; 46(4): 3779-3800, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38319539

RESUMEN

Cerebral small vessel diseases (CSVD) are neurological disorders associated with microvessels, manifested pathologically as white matter (WM) changes and cortical microbleeds, with hypertension as a risk factor. Additionally, a high-fat diet (HFD) can affect peripheral vessel health. Our study explored how HFD affects cerebral small vessels in normotensive WKY, hypertensive SHR, and SHR/SP rats. The MRI results revealed that HFD specifically increased WM hyperintensity in SHR/SP rats. Pathologically, it increased WM pallor and vacuolation in SHR and SHR/SP rats. Levels of blood-brain barrier (BBB) protein claudin 5 were decreased in SHR and SHR/SP compared to WKY, with HFD having minimal impact on these levels. Conversely, collagen IV levels remained consistent among the rat strains, which were increased by HFD. Consequently, HFD caused vessel leakage in all rat strains, particularly within the corpus callosum of SHR/SP rats. To understand the underlying mechanisms, we assessed the levels of hypoxia-inducible factor-1α (HIF-1α), Gp91-phox, and neuroinflammatory markers astrocytes, and microglia were increased in SHR and SHR/SP compared to WKY and were further elevated by HFD in all rat strains. Gp91-phox was also increased in SHR and SHR/SP compared to WKY, with HFD causing an increase in WKY but little effect in SHR and SHR/SP. In conclusion, our study demonstrates that HFD, in combined with hypertension, intensifies cerebral pathological alterations in CSVD rats. This exacerbation involves increased oxidative stress and HIF-1α in cerebral vessels, triggering neuroinflammation, vascular basement membrane remodeling, IgG leakage, and ultimately WM damage.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Dieta Alta en Grasa , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Animales , Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/etiología , Dieta Alta en Grasa/efectos adversos , Ratas , Masculino , Barrera Hematoencefálica/patología , Imagen por Resonancia Magnética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Claudina-5/metabolismo , Modelos Animales de Enfermedad , Sustancia Blanca/patología , NADPH Oxidasa 2/metabolismo , Hipertensión/patología
11.
Chem Commun (Camb) ; 60(17): 2369-2372, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38318781

RESUMEN

Conventional methods for nitrile synthesis bring inherent environmental risks due to their reliance on oxidants and harsh reaction conditions. Meanwhile, direct electrooxidation of amines to nitriles suffers from low current density. In this study, we propose an innovative indirect electrooxidation strategy for nitrile formation, mediated by Br-/Br2, utilizing a highly efficient CoS2/CoS@Graphite Felt (GF) electrode. Notably, the anodic nitrile generation can be synergistically coupled with the cathodic hydrogen evolution reaction (HER). Through meticulous optimization of reaction parameters, we achieve an impressive 98% selectivity for octanenitrile at a current density of 60 mA cm-2 with a remarkable faradaic efficiency (FE) of 87%. Furthermore, our approach demonstrates excellent versatility, as we successfully evaluate both aliphatic and aromatic primary amines, highlighting its promising potential for practical applications in the field.

12.
Arch Med Sci ; 20(1): 255-266, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38414448

RESUMEN

Introduction: To explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC). Material and methods: The TLSs and four subtypes of TILs were assessed by immunohistochemical (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as valid TLSs. The number of labeled TILs was observed in 5 fields of the most positive cells in the tumor center, invasive edge and within the TLSs, at a field of vision ×40. Results: The TLS distribution was significantly higher in the tumor invasive edge than the tumor center (p < 0.001). Similarly, the infiltrating density of CD8+ T cells and GrB+ T cells was statistically significantly higher in the tumor infiltrating edge than the tumor center. The total number of TILs and FOXP3+ T cells showed a contrary distribution. There was a positive correlation of the density of TLSs and TILs with both the location and the immune phenotype. A higher frequency of TILs and TLSs is often associated with favorable clinicopathologic parameters. Higher numbers of peri-TLSs (p = 0.007), peri-CD8+ (p = 0.019) and peri-GrB+TILs (p = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs (p = 0.019) and TLSs (p = 0.037) were independent prognostic predictor for GC patients. Conclusions: We provide evidence that TLSs were positively associated with lymphocyte infiltration in GC. Thus, the formation of TLSs predicts advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients.

13.
Phytochem Anal ; 35(3): 599-616, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38287705

RESUMEN

INTRODUCTION: Accurate screening and targeted preparative isolation of active substances from natural medicines have long been technical challenges in natural medicine research. OBJECTIVES: This study outlines a new approach for improving the efficiency of natural product preparation, focusing on the rapid and accurate screening of potential active ingredients in Ganoderma lucidum and efficient preparation of lipoxidase inhibitors, with the aim of providing new ideas for the treatment of Alzheimer's disease with G. lucidum. METHODS: The medicinal plant G. lucidum was selected through ultrafiltration coupled with liquid chromatography and mass spectrometry (UF-LC-MS) and computer-assisted screening for lipoxygenase (LOX) inhibitors. In addition, the inhibitory effect of the active compounds on LOX was studied using enzymatic reaction kinetics, and the underlying mechanism is discussed. Finally, based on the earlier activity screening guidelines, the identified ligands were isolated and purified through complex chromatography (high-speed countercurrent chromatography and semi-preparative high-performance liquid chromatography). RESULTS: Five active ingredients, ganoderic acids A, B, C2, D2, and F, were identified and isolated from G. lucidum. We improved the efficiency and purity of active compound preparation using virtual computer screening and enzyme inhibition assays combined with complex chromatography. CONCLUSION: The innovative methods of UF-LC-MS, computer-aided screening, and complex chromatography provide powerful tools for screening and separating LOX inhibitors from complex matrices and provide a favourable platform for the large-scale production of bioactive substances and nutrients.


Asunto(s)
Antineoplásicos , Reishi , Inhibidores de la Lipooxigenasa/farmacología , Cromatografía Líquida de Alta Presión , Distribución en Contracorriente
15.
Phytochem Anal ; 35(1): 116-134, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37798938

RESUMEN

INTRODUCTION: Studies show that Polyporus umbellatus has some pharmacological effects in enhancing immunity and against gout. OBJECTIVES: We aimed to establish new techniques for extraction, biological activity screening, and preparation of xanthine oxidase inhibitors (XODIs) from P. umbellatus. METHODS: First, the extraction of P. umbellatus was investigated using the back propagation (BP) neural network genetic algorithm mathematical regression model, and the extraction variables were optimised to maximise P. umbellatus yield. Second, XODIs were rapidly screened using ultrafiltration, and the change of XOD activity was tested by enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on XOD. Meanwhile, the potential anti-gout effects of the obtained active substances were verified using molecular docking, molecular dynamics simulations, and network pharmacology analysis. Finally, with activity screening as guide, a high-speed countercurrent chromatography (HSCCC) method combined with consecutive injection and two-phase solvent system preparation using the UNIFAC mathematical model was successfully developed for separation and purification of XODIs, and the XODIs were identified using MS and NMR. RESULTS: The results verified that polyporusterone A, polyporusterone B, ergosta-4,6,8(14),22-tetraen-3-one, and ergosta-7,22-dien-3-one of P. umbellatus exhibited high biological affinity towards XOD. Their structures have been further identified by NMR, indicating that the method is effective and applicable for rapid screening and identification of XODIs. CONCLUSION: This study provides new ideas for the search for natural XODIs active ingredients, and the study provide valuable support for the further development of functional foods with potential therapeutic benefits.


Asunto(s)
Polyporus , Xantina Oxidasa , Simulación del Acoplamiento Molecular , Polyporus/química , Inhibidores Enzimáticos/farmacología
16.
J Sep Sci ; 47(1): e2300505, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38135883

RESUMEN

Poria Cum Radix Pini is a rare medicinal fungus that contains several potential therapeutic ingredients. On this basis, a particle swarm mathematical model was used to optimize the extraction process of total triterpenes from P. Cum Radix Pini, and xanthine oxidase inhibitors were screened using affinity ultrafiltration mass spectrometry. Meanwhile, the accuracy of the ultrafiltration assay was verified by molecular docking experiments and molecular dynamics analysis, and the mechanism of action of the active compounds for the treatment of gout was analyzed by enzymatic reaction kinetics and network pharmacology. A high-speed countercurrent chromatography method combined with the consecutive injection and the economical two-phase solvent system preparation using functional activity coefficient of universal quasichemical model (UNIFAC) mathematical model was developed for increasing the yield of target compound. In addition, dehydropachymic acid and pachymic acid were used as competitive inhibitors, and 3-O-acetyl-16alpha-hydroxydehydrotrametenolic acid and dehydrotrametenolic acid were used as mixed inhibitors. Then, activity-oriented separation and purification were performed by high-speed countercurrent chromatography combined with semi-preparative high-performance liquid chromatography and the purity of the four compounds isolated was higher than 90%. It will help to provide more opportunities to discover and develop new potential therapeutic remedies from health care food resources.


Asunto(s)
Gota , Poria , Poria/química , Xantina Oxidasa , Simulación del Acoplamiento Molecular , Cromatografía Líquida de Alta Presión/métodos , Inhibidores Enzimáticos/farmacología , Distribución en Contracorriente , Gota/tratamiento farmacológico
17.
RSC Med Chem ; 14(12): 2496-2508, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38107173

RESUMEN

Protein-protein interactions (PPIs) control many essential biological pathways which are often misregulated in disease. As such, selective PPI modulators are desirable to unravel complex functions of PPIs and thus expand the repertoire of therapeutic targets. However, the large size and relative flatness of PPI interfaces make them challenging molecular targets for conventional drug modalities, rendering most PPIs "undruggable". Therefore, there is a growing need to discover innovative molecules that are able to modulate crucial PPIs. Peptides are ideal candidates to deliver such therapeutics attributed to their ability to closely mimic structural features of protein interfaces. However, their inherently poor proteolysis resistance and cell permeability inevitably hamper their biomedical applications. The introduction of a constraint (i.e., peptide cyclization) to stabilize peptides' secondary structure is a promising strategy to address this problem as witnessed by the rapid development of cyclic peptide drugs in the past two decades. Here, we comprehensively review the recent progress on stabilized cyclic peptides in targeting challenging PPIs. Technological advancements and emerging chemical approaches for stabilizing active peptide conformations are categorized in terms of α-helix stapling, ß-hairpin mimetics and macrocyclization. To discover potent and selective ligands, cyclic peptide library technologies were updated based on genetic, biochemical or synthetic methodologies. Moreover, several advances to improve the permeability and oral bioavailability of biologically active cyclic peptides enable the de novo development of cyclic peptide ligands with pharmacological properties. In summary, the development of cyclic peptide-based PPI modulators carries tremendous promise for the next generation of therapeutic agents to target historically "intractable" PPI systems.

18.
Dalton Trans ; 52(45): 16661-16669, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37910402

RESUMEN

Because of their remarkable qualities including changeable chemical composition, good redox characteristics, and ease of manufacture, non-enzymatic glucose sensors based on metallic hydroxides have attracted much interest. However, enhancement of their peroxidase-like catalytic activity is challenging due to their poor substrate affinity and low electrical conductivity, affecting electron transfer. Herein, a three-dimensional hierarchical architecture of Ni/Co-decorated-Fe layered double hydroxide (NiCoFe-LDH) was straightforwardly constructed on Fe foam (FF) via a feasible corrosion strategy, and the non-enzymatic glucose sensing properties of the NiCoFe-LDH/FF electrode were investigated. In the linear detection range of 0.010-0.1 mM, the electrode exhibits an extreme sensitivity of 5717 µA mM-1 cm-2 with a low threshold for glucose determination of 2.61 µM (S/N = 3) and a short reaction time (∼2 s), which is ascribed to its specific intertwined nanosheet-like morphology with rich electron transfer passages that enhance conductivity and improve the accessibility to more active catalytic sites for glucose oxidation. Moreover, the electrode shows excellent selectivity, good stability, and promising practicality for glucose detection in actual serum samples. These results indicate that the feasible corrosion approach towards the simple synthesis of trimetallic layered double hydroxide electrodes results in improved affinity and stability, holding new prospects for achieving reliable, cost-efficient, and eco-friendly non-enzymatic glucose detection.


Asunto(s)
Glucosa , Hidróxidos , Corrosión , Hidróxidos/química , Oxidación-Reducción
19.
Chem Sci ; 14(43): 12238-12245, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37969591

RESUMEN

Zero-dimensional (0D) hybrid metal halide (HMH) glasses are emerging luminescent materials and have gained attention due to their transparent character and ease of processing. However, the weakening of photoluminescence quantum efficiency from crystal to glass phases poses limitations for photonics applications. Here we develop high-performance glass-ceramic (G-C) scintillators via in situ recrystallization from 0D HMH glass counterparts composed of distinct organic cations and inorganic anions. The G-C scintillators maintain excellent transparency and exhibit nearly 10-fold higher light yields and lower detection limits than those of glassy phases. The general in situ recrystallization within the glass component by a facile heat treatment is analyzed via combined experimental elaboration and structural/spectral characterization. Our results on the development of G-Cs can initiate more exploration on the phase transformation engineering in 0D HMHs, and therefore make them highly promising for large-area scintillation screen applications.

20.
Anal Chim Acta ; 1284: 341990, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37996164

RESUMEN

MicroRNAs (miRNAs) are important biomacromolecules used as biomarkers for the diagnosis of several diseases. However, current detection strategies are limited by expensive equipment and complicated procedures. Here, we develop a portable, sensitive, and stable (Eu-MOF)-based sensing platform to detect miRNA via smartphone. The Eu-MOF absorbs the carboxyfluorescein (FAM)-tagged probe DNA (pDNA) to generate hybrid pDNA@Eu-MOF, which can efficiently quench the fluorescence of FAM through a photoinduced electron transfer (PET) process. When integrated with a smartphone, the nonemissive pDNA@ Eu-MOF hybrid could be utilized as a portable and sensitive platform to sense miRNA (miR-892b) with a detection limit of 0.32 pM, which could be even distinguished by the naked eye. Moreover, this system demonstrates high selectivity for identifying miRNA family members with single-base mismatches. Furthermore, the expression levels of miRNA in cancer cell samples could be analyzed accurately. Therefore, the proposed method offers a promising guideline for the design of MOF-based sensing strategies and expands their potential applications for diagnostic purposes.


Asunto(s)
Estructuras Metalorgánicas , MicroARNs , MicroARNs/genética , Luminiscencia , Sondas de ADN/genética , Fluorescencia , Límite de Detección
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA