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1.
Nature ; 601(7892): 245-251, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34912119

RESUMEN

Pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) in plants enable them to respond to pathogens by activating the production of defence metabolites that orchestrate immune responses1-4. How the production of defence metabolites is promoted by immune receptors and coordinated with broad-spectrum resistance remains elusive. Here we identify the deubiquitinase PICI1 as an immunity hub for PTI and ETI in rice (Oryza sativa). PICI1 deubiquitinates and stabilizes methionine synthetases to activate methionine-mediated immunity principally through biosynthesis of the phytohormone ethylene. PICI1 is targeted for degradation by blast fungal effectors, including AvrPi9, to dampen PTI. Nucleotide-binding domain, leucine-rich-repeat-containing receptors (NLRs) in the plant immune system, such as PigmR, protect PICI1 from effector-mediated degradation to reboot the methionine-ethylene cascade. Natural variation in the PICI1 gene contributes to divergence in basal blast resistance between the rice subspecies indica and japonica. Thus, NLRs govern an arms race with effectors, using a competitive mode that hinges on a critical defence metabolic pathway to synchronize PTI with ETI and ensure broad-spectrum resistance.


Asunto(s)
Oryza , Enfermedades de las Plantas , Metionina , Oryza/genética , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Inmunidad de la Planta/genética , Plantas , Transducción de Señal/genética
2.
Hepatobiliary Pancreat Dis Int ; 22(1): 72-80, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35428596

RESUMEN

BACKGROUND: Early singular nodular hepatocellular carcinoma (HCC) is an ideal surgical indication in clinical practice. However, almost half of the patients have tumor recurrence, and there is no reliable prognostic prediction tool. Besides, it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it. It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus, to improve the outcomes of these patients. The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival (RFS) and overall survival (OS) in patients with singular nodular HCC by integrating the clinical data and radiological features. METHODS: We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital (EHBH). They all met the surgical indications and underwent radical resection. We randomly divided the patients into the training cohort (n =132) and the validation cohort (n = 79). We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS. By analyzing the receiver operating characteristic (ROC) curve, the discrimination accuracy of the models was compared with that of the traditional predictive models. RESULTS: Our RFS model was based on HBV-DNA score, cirrhosis, tumor diameter and tumor capsule in imaging. RFS nomogram had fine calibration and discrimination capabilities, with a C-index of 0.74 (95% CI: 0.68-0.80). The OS nomogram, based on cirrhosis, tumor diameter and tumor capsule in imaging, had fine calibration and discrimination capabilities, with a C-index of 0.81 (95% CI: 0.74-0.87). The area under the receiver operating characteristic curve (AUC) of our model was larger than that of traditional liver cancer staging system, Korea model and Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma, indicating better discrimination capability. According to the models, we fitted the linear prediction equations. These results were validated in the validation cohort. CONCLUSIONS: Compared with previous radiography model, the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC. Our models may preoperatively identify patients with high risk of recurrence. These patients may benefit from neoadjuvant therapy which may improve the patients' outcomes.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Pronóstico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Nomogramas , Hepatectomía/métodos , Radiografía
3.
Nanotechnology ; 32(10): 105201, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33217749

RESUMEN

Recently emerging spintronic terahertz (THz) emitters, featuring many appreciable merits such as low-cost, high efficiency, ultrabroadband, and ease of integration, offer multifaceted capabilities not only in understanding the fundamental ultrafast magnetism physics but also for exploring multifarious practical applications. Integration of various flexible and tunable functions at the source such as polarization manipulation, amplitude tailoring, phase modulation, and radiation beam steering with the spintronic THz emitters and their derivatives can yield more compact and elegant devices. Here, we demonstrate a monolithic metamaterial integrated onto a W/CoFeB/Pt THz nanoemitter for a purpose-designed functionality of the electromagnetically induced transparency analog. Through elaborate engineering the asymmetry degree and geometric parameters of the metamaterial structure, we successfully verified the feasibility of monolithic modulations for the radiated THz waves. The integrated device was eventually compared with a set of stand-alone metamaterial positioning scenarios, and the negligible frequency difference between two of the positioning schemes further manifests almost an ideal realization of the proposed monolithic integrated metamaterial device with a spintronic THz emitter. We believe that such adaptable and scalable devices may make valuable contributions to the designable spintronic THz devices with pre-shaping THz waves and enable chip-scale spintronic THz optics, sensing, and imaging.

4.
Biomacromolecules ; 21(12): 4933-4944, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33210916

RESUMEN

In this work, biocompatible and degradable biohybrid microgels based on chitosan and dextran were synthesized for drug delivery applications. Two kinds of bio-based building blocks, alkyne-modified chitosan and azide-modified dextran, were used to fabricate microgels via single-step cross-linking in water-in-oil emulsions. The cross-linking was initiated in the presence of copper(II) without the use of any extra cross-linkers. A series of pH-responsive and degradable microgels were successfully synthesized by varying the degree of cross-links. The microgels were characterized using 1H NMR and FTIR spectroscopy which proved the successful cross-linking of alkyne-modified chitosan and azide-modified dextran by copper(II)-mediated click reaction. The obtained microgels exhibit polyampholyte character and can carry positive or negative charges in aqueous solutions at different pH values. Biodegradability of microgels was shown at pH 9 or in the presence of Dextranase due to the hydrolysis of carbonate esters in the microgels or 1,6-α-glucosidic linkages in dextran structure, respectively. Furthermore, the microgels could encapsulate vancomycin hydrochloride (VM), an antibiotic, with a high loading of approximately 93.67% via electrostatic interactions. The payload could be released in the presence of Dextranase or under an alkaline environment, making the microgels potential candidates for drug delivery, such as colon-specific drug release.


Asunto(s)
Quitosano , Dextranos , Microgeles , Alquinos , Azidas , Reacción de Cicloadición
5.
Soft Matter ; 15(42): 8589-8602, 2019 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-31642835

RESUMEN

In this work, we synthesized electroactive and degradable microgels based on biomacromolecular building blocks, which enable the controlled release of therapeutic drugs. Functional chitosan-poly(hydroquinone) (Ch:PHQ) microgels exhibiting redox-active and pH-sensitive properties were synthesized by an oxidative polymerization in an inverse miniemulsion system. Physically crosslinked microgels were formed by polymerization of hydroquinone in the presence of chitosan through the formation of hydrogen bonds between PHQ and Ch. A series of microgel samples with variable Ch : PHQ ratios were synthesized. These obtained microgels exhibit pH-responsive properties due to the protonation/deprotonation of amino-groups of chitosan in the microgel system. Poly(hydroquinone) is a redox-active polymer exhibiting a two-electron/proton-transfer behavior and conveys this property to the microgels as confirmed by cyclic voltammetry. In addition, the microgels can be switched by electrochemical means: they swell in the oxidized state or shrink in the reduced state. In the presence of urea or lysozyme, the microgels undergo a fast degradation due to the disruption of hydrogen bonds acting as physical crosslinks in the microgel networks or due to the cleavage of glucosidic linkages of the incorporated chitosan scaffold, respectively. Doxorubicin (DOX), an anticancer drug, could be effectively encapsulated into the microgels and released in the presence of an enzyme, indicating that these biodegradable microgels could be used as drug delivery vehicles for tumor cells.


Asunto(s)
Quitosano/química , Hidroquinonas/química , Microgeles/química , Polímeros/química , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Técnicas Electroquímicas , Fibroblastos/citología , Enlace de Hidrógeno , Ratones , Muramidasa/química , Urea/química
6.
Virus Genes ; 52(1): 99-106, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26748656

RESUMEN

The non-structural 5A (NS5A) protein of classical swine fever virus (CSFV) is proven to be involved in viral replication and can also modulate cellular signaling and host cellular responses via to its ability to interact with various cellular proteins. FKBP8 is also reported to promote virus replication. Here, we show that NS5A specifically interacts with FKBP8 through coimmunoprecipitation and GST-pulldown studies. Additionally, confocal microscopy study showed that NS5A and FKBP8 colocalized in the cytoplasm. Overexpression of FKBP8 via the eukaryotic expression plasmid pDsRED N1 significantly promoted viral RNA synthesis. The cells knockdown of FKBP8 by lentivirus-mediated shRNA markedly decreased the virus replication when infected with CSFV. These data suggest that FKBP8 plays a critical role in the viral life cycle, particularly during the virus RNA replication period. The investigation of FKBP8 protein functions may be beneficial for developing new strategies to treat CSFV infection.


Asunto(s)
Virus de la Fiebre Porcina Clásica/fisiología , Proteínas de Unión a Tacrolimus/metabolismo , Proteínas no Estructurales Virales/metabolismo , Replicación Viral , Animales , Secuencia de Bases , ADN , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Datos de Secuencia Molecular , Unión Proteica , Porcinos
7.
J Gen Virol ; 96(Pt 7): 1732-45, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25805409

RESUMEN

Classical swine fever is one of the most important swine diseases worldwide and has tremendous socioeconomic impact. In this study, we focused on the signalling pathways of Toll-like receptors (TLRs) because of their roles in the detection and response to viral infections. To this end, two classical swine fever virus (CSFV) strains, namely the highly virulent CSFV Shimen strain and the avirulent C strain (a vaccine strain), were employed, and the expression of 19 immune effector genes was analysed by real-time PCR, Western blot analyses, ELISA and flow cytometry analyses. In vitro experiments were conducted with porcine monocyte-derived macrophages (pMDMs). The results showed that the mRNA and protein levels of TLR2, TLR4 and TLR7 were upregulated in response to CSFV infection, but TLR3 remained unchanged, and was downregulated after infection with the C strain and the Shimen virus, respectively. Furthermore, TLR3-mediated innate immune responses were inhibited in Shimen-strain-infected pMDMs by stimulation with poly(I : C). Accordingly, comprehensive analyses were performed to detect TLR-dependent cytokine responses and the activation of TLR signalling elements. CSFV infection induced mitogen-activated protein kinase activation, but did not elicit NFκB activation, thereby affecting the production of pro-inflammatory cytokines. The Shimen strain infection resulted in a significant activation of IFN regulatory factor IRF7 and suppression of IRF3. These data provided clues for understanding the effect of CSFV infection on the TLR-mediated innate immune response and associated pathological changes.


Asunto(s)
Virus de la Fiebre Porcina Clásica/inmunología , Expresión Génica , Interacciones Huésped-Patógeno , Macrófagos/inmunología , Macrófagos/virología , Receptores Toll-Like/biosíntesis , Animales , Western Blotting , Células Cultivadas , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Perfilación de la Expresión Génica , Reacción en Cadena en Tiempo Real de la Polimerasa , Porcinos
8.
J Gen Virol ; 95(Pt 12): 2693-2699, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25146005

RESUMEN

Classical swine fever virus (CSFV) has a tropism for vascular endothelial cells and immune system cells. The process and release of pro-inflammatory cytokines, including IL-1ß and IL-18, is one of the fundamental reactions of the innate immune response to viral infection. In this study, we investigated the production of IL-1ß from macrophages following CSFV infection. Our results showed that IL-1ß was upregulated after CSFV infection through activating caspase-1. Subsequent studies demonstrated that reactive oxygen species may not be involved in CSFV-mediated IL-1ß release. Recently, research has indicated a novel mechanism by which inflammasomes are triggered through detection of activity of viroporin. We further demonstrated that CSFV viroporin p7 protein induced IL-1ß secretion which could be inhibited by the ion channel blocker amantadine and also discovered that p7 protein was a short-lived protein degraded by the proteasome. Together, our observations provided an insight into the mechanism of CSFV-induced inflammatory responses.


Asunto(s)
Virus de la Fiebre Porcina Clásica/fisiología , Interleucina-1beta/metabolismo , Macrófagos/virología , Proteínas Virales/farmacología , Animales , Caspasa 1/genética , Caspasa 1/metabolismo , Células Cultivadas , Interleucina-1beta/genética , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Porcinos , Proteínas Virales/metabolismo
9.
Vet Res ; 45: 48, 2014 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-24758593

RESUMEN

Infection of domestic swine with the highly virulent Shimen strain of classical swine fever virus causes hemorrhagic lymphadenitis and diffuse hemorrhaging in infected swine. We analyzed patterns of gene expression for CSFV Shimen in swine umbilical vein endothelial cells (SUVECs). Transcription of the vascular endothelial growth factor (VEGF) C gene (VEGF-C) and translation of the corresponding protein were significantly up-regulated in SUVECs. Our findings suggest that VEGF-C is involved in mechanisms of acute infection caused by virulent strains of CSFV.


Asunto(s)
Virus de la Fiebre Porcina Clásica/fisiología , Virus de la Fiebre Porcina Clásica/patogenicidad , Peste Porcina Clásica/genética , Enfermedades de los Porcinos/genética , Factor C de Crecimiento Endotelial Vascular/genética , Animales , Peste Porcina Clásica/virología , Virus de la Fiebre Porcina Clásica/genética , Células Endoteliales/metabolismo , Perfilación de la Expresión Génica/veterinaria , Regulación Viral de la Expresión Génica , Porcinos , Enfermedades de los Porcinos/virología , Venas Umbilicales/metabolismo , Venas Umbilicales/virología , Regulación hacia Arriba , Factor C de Crecimiento Endotelial Vascular/metabolismo , Virulencia
10.
Int J Biol Macromol ; 263(Pt 1): 130269, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38387630

RESUMEN

For improving the emulsion stability of rice bran protein (RBP), RBP was modified by different concentrations of epigallocatechin-3-gallate (EGCG) in the presence of soybean protein isolate (SPI), and RBP-EGCG-SPI conjugate was prepared by alkaline pH-shifting. The results showed that the addition of EGCG led to an increase in the bound phenol content and the flexibility of the secondary structure, a decrease in the free sulfhydryl and disulfide bond content of the RBP-EGCG-SPI conjugate. EGCG covalently bound to RBP and SPI through non-disulfide bonds. When the concentration of EGCG was 10 % (w/v), the emulsifying activity index and emulsion stability index of conjugate reached the maximum value (36.61 m2/g and 255.61 min, respectively), and the conjugate had the best emulsion stability. However, an EGCG concentration above 10 % (w/v) negatively affected the emulsion stability, with increasing particle size due to protein aggregation. Summarily, the modification of EGCG improved the emulsion stability of conjugate by regulating the spatial structure of RBP-EGCG-SPI conjugate. The work provided an important guide to further improve the emulsion stability of RBP.


Asunto(s)
Catequina , Catequina/análogos & derivados , Oryza , Proteínas de Soja/química , Emulsiones/química , Oryza/metabolismo , Catequina/química
11.
Food Chem ; 460(Pt 1): 140617, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39067385

RESUMEN

Both rice bran (RB) rancidity and dephenolization could affect the structural characteristics and phenolics composition of rice bran protein (RBP), thereby affecting RBP digestibility. The synergistic effects of RB rancidity and dephenolization on RBP digestibility were investigated. Excessive RB rancidity (RB stored for 10 d) and non-dephenolization reduced RBP digestibility, while moderate RB rancidity (RB stored for 1 d) combined with dephenolization improved RBP digestibility to a maximum of 74.19%. Dephenolization reduced the antioxidant capacities of RBP digestive products. The digestibility of non-dephenolized RBP (NDRBP) was significantly (P < 0.05) related with its carbonyl content, surface hydrophobicity, and ζ-potential. The digestibility of dephenolized RBP (DRBP) was significantly related with its ß-sheet structure content, surface hydrophobicity, ζ-potential, and average particle size. Overall, moderate RB rancidity combined with dephenolization enhanced RBP digestibility by reducing the non-competitive inhibition of endogenous phenolics on protease and regulating the spatial structural characteristics of RBP.

12.
Sci Rep ; 14(1): 15222, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956233

RESUMEN

The critical value of rock failure is determined by irreversible deformation (inelastic deformation, damage, and other internal dissipation) processes and external conditions before rock failure. Nevertheless, a thorough explanation of the mechanism causing cracks in rock material has not yet been provided. The strain energy theory is applied in this work to assess the initiation of rock cracks and investigate the relationship between energy digestion and rock strength. Firstly, the uniaxial compression test was conducted on sandstone samples under quasi-static loading conditions and the results of energy evolution, non-linear cumulative digestion, and stored ultimate energy were obtained. Then, a novel algorithm for assessing the initiation of rock cracks has been put forth. The concept of energy digestion index (EDI), which is the ratio of digested energy over the external loading energy, has been developed to characterize the energy absorption capacity of rock material. The result shows a relationship between the maximum growth rate of energy digestion and the increasing rate of variable elasticity modulus and crack initiation. The mechanical characteristics and peak strength of the rock material are negatively correlated with the EDI. By monitoring the digested energy status, an evaluation of the residual strength is introduced based on the relationships, which will initiate further research into in-situ monitoring and failure prediction.

13.
Food Chem ; 443: 138611, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38309025

RESUMEN

The effects of rice bran rancidity-induced protein oxidation and heating time on the stability of rice bran protein fibril aggregates (RBPFA)-high internal phase Pickering emulsions (HIPPEs) were investigated. The optimal conditions for RBPFA-HIPPEs were 8 mg/mL RBPFA with an oil phase volume fraction of 75 %. Moderate oxidation (rice bran stored for 3 d) and moderate heating (8 h) enhanced the wettability, flexibility, diffusion rate, and adsorption rate of RBPFA, meanwhile, the rheological properties of RBPFA-HIPPEs increased. RBPFA-HIPPEs could be stably stored for 50 d at 25 °C. Moderate oxidized and moderate heated RBPFA-stabilized HIPPEs could remain stable after heat treatment and could be re-prepared after freeze-thaw (3 cycles). Additionally, the stability of RBPFA-HIPPEs was significantly related to the structural characteristics and interfacial properties of RBPFA. Overall, moderate oxidation and moderate heating enhanced the storage, thermal, and freeze-thaw stability of RBPFA-HIPPEs by improving the interfacial properties of RBPFA.


Asunto(s)
Oryza , Emulsiones/química , Agregado de Proteínas , Adsorción , Oxidación-Reducción , Tamaño de la Partícula
14.
Int J Biol Macromol ; 271(Pt 2): 132663, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38797291

RESUMEN

This study investigated the release of aromatic compounds with distinct functional groups within bilayer microcapsules. Bilayer microcapsules of four distinctive core materials (benzyl alcohol, eugenol, cinnamaldehyde, and benzoic acid) were synthesized via freeze-drying. Chitosan (CS) and sodium alginate (ALG) were used as wall materials. CS concentration, using orthogonal experiments with the loading ratio as a metric. Under optimal conditions, three other types of microcapsules (cinnamic aldehyde, benzoic acid, and benzyl alcohol) were obtained. The four types of microcapsules were characterized using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), and thermogravimetric analysis (TGA), and their sustained release characteristics were evaluated. The optimal conditions were: CS dosage, 1.2 %; CS-to-eugenol mass ratio, 1:2; and CS-to-ALG mass ratio, 1:1. By comparing the IR spectra of the four types of microcapsules, wall material, and core material, the core materials were revealed to be encapsulated within the wall material. SEM results revealed that the granular protuberances on the surface of the microcapsules were closely aligned and persistent when magnified 2000×. The TEM results indicated that all four microcapsules had a spherical and bilayer structure. The thermal stability and sustained release results showed that the four microcapsules were more resilient and less volatile than the four core materials. The release conformed to first-order kinetics, and the release ratios of the four microcapsules were as follows: benzyl alcohol microcapsules Ëƒ eugenol microcapsules Ëƒ cinnamaldehyde microcapsules Ëƒ benzoic acid microcapsules. The prepared bilayer microcapsules encapsulated four different core materials with good sustained release properties.


Asunto(s)
Alginatos , Cápsulas , Quitosano , Preparaciones de Acción Retardada , Liberación de Fármacos , Quitosano/química , Alginatos/química , Preparaciones de Acción Retardada/química , Eugenol/química , Ácido Benzoico/química , Espectroscopía Infrarroja por Transformada de Fourier , Acroleína/química , Acroleína/análogos & derivados , Portadores de Fármacos/química , Termogravimetría
15.
Neuroscience ; 544: 50-63, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38387733

RESUMEN

The M1 polarization of microglia, followed by the production of pro-inflammatory mediators, hinders functional recovery after spinal cord injury (SCI). Our previous study has illuminated that specificity protein 1 (Sp1) expression is increased following SCI, whereas the function and regulatory mechanism of Sp1 during M1 polarization of microglia following SCI remain unknown. RNA binding protein, HuR, has been shown to be up-regulated in the injured spinal cord through analysis of the GEO database. Further investigation using Chip-Atlas data suggests a binding between Sp1 and HuR. Emerging evidence indicates that HuR plays a pivotal role in neuroinflammation after SCI. In this research, Sp1 and HuR levels in mice with SCI and BV2 cells treated with lipopolysaccharide (LPS) was determined by using quantitative real-time polymerase chain reaction and Western blotting techniques. A series of in vitro assays were performed to investigate the function of Sp1 during M1 polarization of microglia. The association between Sp1 and its target gene HuR was confirmed through gene transfection and luciferase reporter assay. Enhanced expression of HuR was observed in both SCI mice and LPS-treated BV2 cells, while Sp1 knockdown restrained M1 polarization of microglia and its associated inflammation by inhibiting the NF-κB signaling pathway. Silencing Sp1 also suppressed microglia activation and its mediated inflammatory response, which could be reversed by overexpression of HuR. In conclusion, silencing Sp1 restrains M1 polarization of microglia through the HuR/NF-κB axis, leading to neuroprotection, and thus promotes functional restoration following SCI.


Asunto(s)
FN-kappa B , Factor de Transcripción Sp1 , Traumatismos de la Médula Espinal , Animales , Ratones , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Microglía/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Factor de Transcripción Sp1/genética , Factor de Transcripción Sp1/metabolismo
16.
Int J Biol Macromol ; 253(Pt 5): 127019, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37739282

RESUMEN

As a plant-derived drug, piperine possesses therapeutic efficacy for many diseases, but its inherent low solubility and bioavailability have greatly limited its clinical use. Herein, we extracted piperine from black pepper, optimized the structure of piperine to prepare various derivatives, and then explored the anticancer activity of these derivatives. Piperine and its derivatives have high anticancer selectivity against 4T1 cells, exhibiting obvious anticancer properties even at a low concentration of 100 µg/mL. Furthermore, the physicochemical properties of piperine and its derivatives were investigated using density functional theory, demonstrating their considerable biological activity. Moreover, the chitosan-based microgels were prepared to encapsulate the hydrophobic piperine derivative with a high loading efficiency of 81.7 % to overcome the low water solubility of the piperine derivative. It is worth noting that excessive glutathione in tumor cells triggers the degradation of microgels and realizes controllable drug release of up to 72.3 %. Due to its excellent properties, chitosan-based microgels loaded with the piperine derivative can obtain good anticancer behavior of approximately 13.14 % cell viability against 4T1 cells. Therefore, the chitosan-based microgels overcome the low water solubility of the piperine derivative through encapsulation and thus further augment their delivery efficiency and cell internalization capability to realize excellent anticancer activity. This work demonstrates the enhanced anticancer efficacy of the hydrophobic plant-derived drug by means of structural optimization of piperine and chitosan-based microgels with boosted drug delivery.


Asunto(s)
Quitosano , Microgeles , Quitosano/química , Sistemas de Liberación de Medicamentos , Agua
17.
Burns ; 49(4): 889-900, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35850880

RESUMEN

OBJECTIVE: Curcumin, a natural extract from the rhizomes of Curcuma longa, is also known as a curcuminoid. Curcumin has been studied as a therapeutic drug for wound healing because of its anti-inflammatory, anti-oxidant, and anti-bacterial activities. However, the detailed mechanism of curcumin in wound healing is not clear. It is well-known that the skin is the largest organ in humans and prevents tissues from damage, including infection, radiation, and mechanical damage. Wound healing of the skin is a complex physiological regulation process requiring various cell types and cytokines; hence, wound healing, including surgery and care, incurs a huge expenditure each year. Transient receptor potential cation channel subfamily M member 7 (TRPM7) regulates multiple physiological and pharmacological processes through its channel and kinase activities. In addition, TRPM7 regulates cell adhesion, migration, and anti-oxidative activity, thereby playing a regulatory role in the wound healing process. This study aimed to explore the function of curcumin in the wound healing process. METHODS: We first established TRPM7 overexpression and knockdown models in fibroblasts using lentivirus. CCK-8 and wound healing assays were used to clarify whether overexpression of TRPM7 promoted proliferation and migration in fibroblasts. Expression of target genes and proteins was detected using qPCR and western blotting. Concentrations of migration-related cytokines were measured using ELISA. RESULTS: Proliferation and migration of fibroblasts increased after curcumin treatment and was further enhanced after overexpression of TRPM7. In addition, expression of proliferation-related genes and proteins was elevated after TRPM7 overexpression. Further, the secretion of migration-related cytokines was elevated after TRPM7 overexpression. CONCLUSION: Curcumin treatment promoted proliferation and migration of fibroblasts, and these effects were mediated by the signal transducer and activator of transcription 3 (STAT3)/SMAD family member 3/hypoxia-inducible factor 1 subunit alpha signaling pathway. Thus, we conclude that overexpression of TRPM7 might contribute to wound healing.


Asunto(s)
Quemaduras , Curcumina , Canales Catiónicos TRPM , Humanos , Quemaduras/metabolismo , Curcumina/metabolismo , Curcumina/farmacología , Citocinas/metabolismo , Fibroblastos/metabolismo , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Proteína smad3/metabolismo , Proteína smad3/farmacología , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/farmacología , Canales Catiónicos TRPM/metabolismo , Cicatrización de Heridas
18.
Int J Biol Macromol ; 252: 126389, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37611687

RESUMEN

During recent years, antibiotic-resistant bacteria have rapidly emerged owing to the irrational use of antibiotics, rendering a global problem. Currently, few studies introduce customized antibacterial nanoplatforms to overcome antibiotic-resistance according to specific characteristic of bacteria, rather than abuse of antibiotic. Herein, with regard to personalized antibacterial nanoplatform, we design a novel antibiotic delivery nanocarrier composed of polyaniline-grafted-chitosan, presenting pH-responsive, conductive, photothermal, and biodegradable properties. After treatment with divalent anion (SO42-), the negatively charged nanocarriers are obtained for improving the loading efficacy of cationic vancomycin. Meanwhile, the controlled vancomycin release is achieved by lysozyme-triggered degradation of the nanocarrier. With the assistance of photothermal effect, the photothermal-assisted antibacterial effect of the nanocarriers have been effectively enhanced rather than that of a single antibacterial effect of vancomycin. Owing to the low heat resistance of Escherichia coli, photothermal effect can break the antibiotic-resistant bacteria membrane to render the convenient antibiotic entry, leading to the improved antibacterial efficacy. Therefore, the customization of a photothermal-assisted antibacterial on account of the characteristic of specific bacteria can definitely expand our arsenal for enhancing the antibacterial effect against antibiotic-resistant bacteria.


Asunto(s)
Quitosano , Microgeles , Vancomicina/farmacología , Quitosano/farmacología , Antibacterianos/farmacología , Escherichia coli
19.
J Adv Res ; 43: 87-96, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36585117

RESUMEN

INTRODUCTION: High-dose drug administration for the conventional treatment of inflammatory bowel disease induces cumulative toxicity and serious side effects. Currently, few reports have introduced smart carriers for intestinal inflammation targeting toward the treatment of inflammatory bowel disease. OBJECTIVES: For the unique lysozyme secretory microenvironment of the inflamed intestine, vancomycin-loaded chitosan-polyaniline microgels (CH-PANI MGs) were constructed for lysozyme-triggered VM release. METHODS: Aniline was first grafted to chitosan to form polymers that were crosslinked by glutaraldehyde to achieve CH-PANI MGs using the inverse (water-in-oil) miniemulsion method. Interestingly, CH-PANI MGs exhibit polyampholyte behaviour and display charge-reversible behaviour (positive to negative charges) after treatment with a NaCl solution. RESULTS: The formed negatively charged N-CH-PANI MG aqueous solution is employed to load cationic vancomycin with a satisfactory loading efficiency of 91.3%, which is significantly higher than that of chitosan-based MGs. Moreover, N-CH-PANI MGs present lysozyme-triggered biodegradation and controllable vancomycin release upon the cleavage of glycosidic linkages of chitosan. In the simulated inflammatory intestinal microenvironment, vancomycin is rapidly released, and the cumulative release reaches approximately 76.9%. Remarkably, N-CH-PANI@VM MGs not only exhibit high resistance to harsh gastric acidity but also prevent the premature leakage of vancomycin in the healthy gastrointestinal tract. Encouragingly, the N-CH-PANI@VM MGs show obvious antibacterial activity against Staphylococcus aureus at a relatively low concentration of 20 µg/mL. CONCLUSION: Compared to other pH-responsive carriers used to treat inflammatory bowel disease, the key advantage of lysozyme-responsive MGs is that they further specifically identify healthy and inflammatory intestines, achieving efficient inflammatory bowel disease treatment with few side effects. With this excellent performance, the developed smart MGs might be employed as a potential oral delivery system for inflammatory bowel disease treatment.


Asunto(s)
Quitosano , Enfermedades Inflamatorias del Intestino , Microgeles , Quitosano/química , Quitosano/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Microgeles/química , Microgeles/uso terapéutico , Muramidasa , Vancomicina/administración & dosificación , Vancomicina/farmacología , Vancomicina/uso terapéutico , Sistemas de Liberación de Medicamentos
20.
Food Res Int ; 172: 113166, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37689915

RESUMEN

The emulsion carriers which prepared by rice bran protein (RBP) with different oxidation extents were utilized to deliver ß-carotene (BC). The effects of RBP oxidation extent on stability and bioaccessibility of BC in rice bran protein emulsion (RBPE) were investigated by measuring the droplet size, microstructure, digestive stability, cellular antioxidant, and delivery property of BC-RBPE. The results showed that BC-RBPE prepared by moderately oxidized RBP (extracted from rice bran with a storage time of 5 d) presented excellent digestive stability and delivery property during gastrointestinal digestion. The particle size of initial BC-RBPE, BC-RBPE after gastric digestion, and BC-RBPE after intestinal digestion were 509.73, 2149.33, and 997.82 nm, respectively. Compared with free BC suspension, the BC retention after gastric digestion and the BC bioavailability of BC-RBPE prepared by moderately oxidized RBP increased by 23.50% and 27.54%, respectively. In addition, the BC cellular antioxidant activity and BC cellular uptake of BC-RBPE prepared by moderately oxidized RBP were significantly higher than that of free BC-suspension, which increased by 29.63% and 13.84%, respectively. In summary, the study showed that oil-in-water emulsion prepared by moderately oxidized protein is a potential delivery system of BC, which can provide a theoretical basis for improving the utilization of protein by adjusting the extent of protein oxidation.


Asunto(s)
Oryza , Antioxidantes , beta Caroteno , Disponibilidad Biológica , Transporte Biológico , Emulsiones
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