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1.
J Am Chem Soc ; 146(9): 6252-6265, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38377559

RESUMEN

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.


Asunto(s)
Neoplasias , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno , Antracenos , Línea Celular Tumoral
2.
Anal Chem ; 96(19): 7697-7705, 2024 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-38697043

RESUMEN

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.


Asunto(s)
Elementos de la Serie de los Lantanoides , Imagen por Resonancia Magnética , Nanopartículas , Polímeros , Semiconductores , Imagen por Resonancia Magnética/métodos , Animales , Elementos de la Serie de los Lantanoides/química , Polímeros/química , Nanopartículas/química , Ratones , Humanos , Gadolinio/química , Luminiscencia , Oxígeno Singlete/química , Itrio/química , Fluoruros/química , Ratones Desnudos
3.
Nano Lett ; 23(7): 2659-2668, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-36940420

RESUMEN

The targeting of tumor metabolism as a novel strategy for cancer therapy has attracted tremendous attention. Herein, we develop a dual metabolism inhibitor, Zn-carnosine metallodrug network nanoparticles (Zn-Car MNs), which exhibits good Cu-depletion and Cu-responsive drug release, causing potent inhibition of both OXPHOS and glycolysis. Notably, Zn-Car MNs can decrease the activity of cytochrome c oxidase and the content of NAD+, so as to reduce ATP production in cancer cells. Thereby, energy deprivation, together with the depolarized mitochondrial membrane potential and increased oxidative stress, results in apoptosis of cancer cells. In result, Zn-Car MNs exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models. The efficacy and therapy of Zn-Car MNs suggest the possibility to overcome the drug resistance caused by metabolic reprogramming in tumors and has potential clinical relevance.


Asunto(s)
Neoplasias de la Mama , Carnosina , Humanos , Femenino , Carnosina/metabolismo , Carnosina/farmacología , Cobre/farmacología , Glucólisis , Zinc
4.
J Nanobiotechnology ; 21(1): 434, 2023 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-37980476

RESUMEN

Manganese-based nanomaterials (Mn-nanomaterials) hold immense potential in cancer diagnosis and therapies. However, most Mn-nanomaterials are limited by the low sensitivity and low efficiency toward mild weak acidity (pH 6.4-6.8) of the tumor microenvironment, resulting in unsatisfactory therapeutic effect and poor magnetic resonance imaging (MRI) performance. This study introduces pH-ultrasensitive PtMn nanoparticles as a novel platform for enhanced ferroptosis-based cancer theranostics. The PtMn nanoparticles were synthesized with different diameters from 5.3 to 2.7 nm with size-dominant catalytic activity and magnetic relaxation, and modified with an acidity-responsive polymer to create pH-sensitive agents. Importantly, R-PtMn-1 (3 nm core) presents "turn-on" oxidase-like activity, affording a significant enhancement ratio (pH 6.0/pH 7.4) in catalytic activity (6.7 folds), compared with R-PtMn-2 (4.2 nm core, 3.7 folds) or R-PtMn-3 (5.3 nm core, 2.1 folds), respectively. Moreover, R-PtMn-1 exhibits dual-mode contrast in high-field MRI. R-PtMn-1 possesses a good enhancement ratio (pH 6.4/pH 7.4) that is 3 or 3.2 folds for T1- or T2-MRI, respectively, which is higher than that of R-PtMn-2 (1.4 or 1.5 folds) or R-PtMn-3 (1.1 or 1.2 folds). Moreover, their pH-ultrasensitivity enabled activation specifically within the tumor microenvironment, avoiding off-target toxicity in normal tissues during delivery. In vitro studies demonstrated elevated intracellular reactive oxygen species production, lipid peroxidation, mitochondrial membrane potential changes, malondialdehyde content, and glutathione depletion, leading to enhanced ferroptosis in cancer cells. Meanwhile, normal cells remained unaffected by the nanoparticles. Overall, the pH-ultrasensitive PtMn nanoparticles offer a promising strategy for accurate cancer diagnosis and ferroptosis-based therapy.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Manganeso/química , Medicina de Precisión , Medios de Contraste/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Imagen por Resonancia Magnética/métodos , Nanopartículas/química , Línea Celular Tumoral , Microambiente Tumoral
5.
Angew Chem Int Ed Engl ; 61(48): e202206074, 2022 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-36222012

RESUMEN

Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T1 /T2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2 -mediated enhancement of key pathways of ferroptosis.


Asunto(s)
Ferroptosis , Nanoestructuras , Humanos , Línea Celular Tumoral , Imagen por Resonancia Magnética , Hipoxia
6.
Angew Chem Int Ed Engl ; 61(31): e202117229, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35460321

RESUMEN

Ferroptosis exhibits potential to damage drug-resistant cancer cells. However, it is still restricted with the "off-target" toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment-triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high-field magnetic resonance imaging (MRI), which enables the real-time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T1 -/T2 -MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI-guided high-specificity ferroptosis therapy.


Asunto(s)
Ferroptosis , Nanopartículas , Neoplasias , Aleaciones , Línea Celular Tumoral , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias/patología , Microambiente Tumoral
7.
Small ; 14(20): e1703816, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29665267

RESUMEN

Lithium-sulfur (Li-S) batteries are investigated intensively as a promising large-scale energy storage system owing to their high theoretical energy density. However, the application of Li-S batteries is prevented by a series of primary problems, including low electronic conductivity, volumetric fluctuation, poor loading of sulfur, and shuttle effect caused by soluble lithium polysulfides. Here, a novel composite structure of sulfur nanoparticles attached to porous-carbon nanotube (p-CNT) encapsulated by hollow MnO2 nanoflakes film to form p-CNT@Void@MnO2 /S composite structures is reported. Benefiting from p-CNTs and sponge-like MnO2 nanoflake film, p-CNT@Void@MnO2 /S provides highly efficient pathways for the fast electron/ion transfer, fixes sulfur and Li2 S aggregation efficiently, and prevents polysulfide dissolution during cycling. Besides, the additional void inside p-CNT@Void@MnO2 /S composite structure provides sufficient free space for the expansion of encapsulated sulfur nanoparticles. The special material composition and structural design of p-CNT@Void@MnO2 /S composite structure with a high sulfur content endow the composite high capacity, high Coulombic efficiency, and an excellent cycling stability. The capacity of p-CNT@Void@MnO2 /S electrode is ≈599.1 mA h g-1 for the fourth cycle and ≈526.1 mA h g-1 after 100 cycles, corresponding to a capacity retention of ≈87.8% at a high current density of 1.0 C.

8.
Acc Chem Res ; 50(10): 2529-2538, 2017 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-28972736

RESUMEN

Despite the development of medical technology, cancer still remains a great threat to the survival of people all over the world. Photothermal therapy (PTT) is a minimally invasive method for selective photothermal ablation of cancer cells without damages to normal cells. Recently, copper chalcogenide semiconductors have emerged as a promising photothermal agent attributed to strong absorbance in the near-infrared (NIR) region and high photothermal conversion efficiency. An earlier study witnessed a rapid increase in their development for cancer therapy, including CuS, Cu2-xSe and CuTe nanocrystals. However, a barrier is that the minimum laser power intensity for effective PTT is still significantly higher than the conservative limit for human skin exposure. Improving the photothermal conversion efficiency and reducing the laser power density has become a direction for the development of PTT. Furthermore, in an effort to improve the therapeutic efficacy, many multimode therapeutic nanostuctures have been formulated by integrating the photothermal agents with antitumor drugs, photosensitizers, or radiosensitizers, resulting in a synergistic effect. Various functional materials also have been absorbed, attached, encapsulated, or coated on the photothermal nanostructures, including fluorescence, computed tomography, magnetic resonance imaging, realizing cancer diagnosis, tumor location, site-specific therapy, and evaluation of therapeutic responses via incorporation of diagnosis and treatment. In this Account, we present an overview of the NIR-responsive photothermal semiconductor nanomaterials for cancer theranostics with a focus on their design and functionalization based on our own work. Our group has developed a series of chalcogenides with greatly improved NIR photoabsorption as photothermal agents, allowing laser exposure within regulatory limits. We also investigated the photothermal bioapplications of hypotoxic oxides including WO3-x, MoO3-x, and RuO2, expanding their applications into a new field of photothermal materials. Furthermore, considering a much more enhanced therapeutic effect of multifunctional nanoagents, our group elaborately designed many nanocomposites, such as core-shell nanoparticles of Fe3O4@Cu2-xS and Cu9S5@mSiO2, based on the integration of photothermal agents with contrast agents or other anticancer medicines, achieving cancer theranostic and synergistic treatment. Ternary compound nanocrystals were also prepared with synthetic simplicity for multimodal imaging-guided therapy for cancer. This Account summarizes our past work, including the design and concept, synthesis, and characterization for in vitro and in vivo applications. Then, we analyzed the tendencies of the NIR-responsive photothermal semiconductor nanomaterials for clinical applications, highlighting their prospects and challenges. We believe that the photothermal technology from the NIR-responsive photothermal semiconductor nanomaterials would promote cancer theranostics to result in giant strides forward in the future.


Asunto(s)
Antineoplásicos/farmacología , Nanopartículas del Metal/química , Neoplasias/tratamiento farmacológico , Semiconductores , Nanomedicina Teranóstica/métodos , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Doxorrubicina/farmacología , Sinergismo Farmacológico , Humanos , Nanopartículas del Metal/efectos de la radiación
9.
Am J Orthod Dentofacial Orthop ; 146(5): 579-86, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25439208

RESUMEN

INTRODUCTION: The aim of this study was to determine how sensitive dental specialists and laypeople are to maxillary incisor crowding when viewed from the front. METHODS: Computer technology was used to create a series of photographs of the incisors of a smiling woman viewed from the front. The photographs showed varying degrees of maxillary incisor crowding classified according to Little's irregularity index (LII). The incisors illustrated in the photos were ranked on a scale from perfect alignment to severely crowded. The rating was done by 4 groups of people: orthodontists, general dentists, laypeople with experience of orthodontic treatment, and laypeople with no history of orthodontic treatment. RESULTS: The orthodontists and the general dentists noted misalignment of 1 central incisor when the LII reached 1.5 mm, whereas the laypeople with or without experience of orthodontic treatment were sensitive to 2.0 mm of crowding. When the LII reached 2.0 mm for 1 lateral incisor, it triggered the orthodontists to consider providing orthodontic treatment, whereas this degree of irregularity was ignored by the general dentists and laypeople. When both central incisors were misaligned, the orthodontists were sensitive to the fact at 2.0 mm of LII, whereas the general dentists and the laypeople with experience of orthodontic treatment became sensitive at 3.0 mm of LII, and the laypeople with no history of orthodontic treatment were sensitive at 4.0 mm of LII. When both lateral incisors were misaligned, the orthodontists noted the crowding at an LII of 3.0 mm, the general dentists became sensitive at an LII of 4.0 mm, whereas both the laypeople with experience of orthodontic treatment and the laypeople with no history of orthodontic treatment ignored it. When the crowding of all maxillary incisors reached an LII of 4 mm, both the orthodontists and the general dentists were alerted to the fact, but both the laypeople with experience of orthodontic treatment and the laypeople with no history of orthodontic treatment were sensitive only to a total incisor crowding equal to an LII of 6.0 mm. CONCLUSIONS: Orthodontists are more critical than other groups when evaluating the misalignment of the maxillary incisors. It appears that the central incisors play a more important role than do the lateral incisors when dental crowding impacts smile esthetics. For all observer groups, it also appears that people are more sensitive to the misalignment of a single tooth than they are to the same level of crowding distributed over multiple teeth.


Asunto(s)
Actitud del Personal de Salud , Actitud Frente a la Salud , Odontólogos/psicología , Incisivo/patología , Maloclusión/psicología , Maxilar/patología , Adulto , Estética Dental , Femenino , Odontología General , Humanos , Masculino , Maloclusión/patología , Ortodoncia , Fotografía Dental , Sonrisa , Corona del Diente/patología , Adulto Joven
10.
Artículo en Inglés | MEDLINE | ID: mdl-37752407

RESUMEN

Magnetic resonance imaging (MRI) is a non-invasive, radiation-free imaging technique widely used for disease detection and therapeutic evaluation due to its infinite penetration depth. Magnetic nanoparticles (MNPs) have unique magnetic and physicochemical properties, making them ideal as contrast agents for MRI. However, the in vivo toxicity of MNPs, resulting from metal ion leakage and long-term accumulation in the reticuloendothelial system (RES), limits their clinical application. To overcome these challenges, there is considerable interest in the development of renal-clearable MNPs that can be completely cleared through the kidney, reducing retention time and potential toxic risks. In this review, we provide an overview of recent advancements in the development of renal-clearable MNPs for disease imaging and treatment. We discuss the factors influencing renal clearance, summarize the types of renal-clearable MNPs, their synthesis methods, and biomedical applications. This review aims to offer comprehensive information for the design and clinical translation of renal-clearable MNPs. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.


Asunto(s)
Nanopartículas de Magnetita , Nanopartículas de Magnetita/química , Medios de Contraste/química , Nanotecnología , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos
11.
BMJ Open ; 14(6): e084703, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950988

RESUMEN

INTRODUCTION: Orthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is effective in the early treatment of patients with class III malocclusion, but the stability of treatment outcomes represents a major concern. Previous studies have suggested that tonsillar hypertrophy can be a risk factor for class III malocclusion and tonsillectomy may prompt the normalisation of dentofacial growth. However, these studies had a low-to-moderate level of evidence. This study was designed to identify the impact of tonsillectomy before orthodontic treatment on the efficacy and stability of Alt-RAMEC/PFM protocols and the sleep quality and oral health in children with anterior crossbite and tonsillar hypertrophy. METHODS AND ANALYSIS: This is a two-arm, parallel-group, superiority cluster randomised controlled trial, with four clinics randomly assigned to the surgery-first arm and the orthodontic-first arm in a 1:1 ratio. The Alt-RAMEC protocol involves alternate activation and deactivation of the expander's jet screw over 6 weeks to stimulate maxillary suture distraction. Patients will be instructed to wear the PFM for a minimum of 14 hours per day. The primary outcomes are changes in Wits appraisal and the degree of maxillary advancement from baseline to the end of orthodontic treatment. Lateral cephalometric radiographs, polysomnography, Obstructive Sleep Apnoea-18 questionnaire and Oral Health Impact Profile-14 questionnaire will be traced, collected and measured. We will recruit 96 patients intofor the study. To assess differences, repeated multilevel linear mixed modelling analyses will be used. ETHICS AND DISSEMINATION: This study has been granted ethical approval by the Ethics Committee of the School & Hospital of Stomatology, Wuhan University (approval No. 2023-D10). Written informed consent will be obtained from the participants and their guardians. The results of the trial will be disseminated through academic conferences and journal publications. TRIAL REGISTRATION NUMBER: ChiCTR2300078833.


Asunto(s)
Hipertrofia , Maloclusión de Angle Clase III , Técnica de Expansión Palatina , Tonsila Palatina , Tonsilectomía , Humanos , Tonsilectomía/métodos , Niño , Maloclusión de Angle Clase III/cirugía , Maloclusión de Angle Clase III/terapia , Tonsila Palatina/patología , Tonsila Palatina/cirugía , Femenino , Aparatos de Tracción Extraoral , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Resultado del Tratamiento , Calidad del Sueño , Adolescente
12.
J Ethnopharmacol ; 328: 118108, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38574780

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala fallax Hemsl. is a traditional folk medicine commonly used by ethnic minorities in the Guangxi Zhuang Autonomous Region, and has a traditional application in the treatment of liver disease. Polygala fallax Hemsl. polysaccharides (PFPs) are of interest for their potential health benefits. AIM OF THIS STUDY: This study explored the impact of PFPs on a mouse model of cholestatic liver injury (CLI) induced by alpha-naphthyl isothiocyanate (ANIT), as well as the potential mechanisms. MATERIALS AND METHODS: A mouse CLI model was constructed using ANIT (80 mg/kg) and intervened with different doses of PFPs or ursodeoxycholic acid. Their serum biochemical indices, hepatic oxidative stress indices, and hepatic pathological characteristics were investigated. Then RNA sequencing was performed on liver tissues to identify differentially expressed genes and signaling pathways and to elucidate the mechanism of liver protection by PFPs. Finally, Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to verify the differentially expressed genes. RESULTS: Data analyses showed that PFPs reduced the levels of liver function-related biochemical indices, such as ALT, AST, AKP, TBA, DBIL, and TBIL. PFPs up-regulated the activities of SOD and GSH, down-regulated the contents of MDA, inhibited the release of IL-1ß, IL-6, and TNF-α, or promoted IL-10. Pathologic characterization of the liver revealed that PFPs reduced hepatocyte apoptosis or necrosis. The RNA sequencing indicated that the genes with differential expression were primarily enriched for the biosynthesis of primary bile acids, secretion or transportation of bile, the reactive oxygen species in chemical carcinogenesis, and the NF-kappa B signaling pathway. In addition, the results of qRT-PCR and Western blotting analysis were consistent with those of RNA sequencing analysis. CONCLUSIONS: In summary, this study showed that PFPs improved intrahepatic cholestasis and alleviated liver damage through the modulation of primary bile acid production, Control of protein expression related to bile secretion or transportation, decrease in inflammatory reactions, and inhibition of oxidative pressure. As a result, PFPs might offer a hopeful ethnic dietary approach for managing intrahepatic cholestasis.


Asunto(s)
Colestasis Intrahepática , Colestasis , Polygala , Ratas , Ratones , Animales , Ratas Sprague-Dawley , 1-Naftilisotiocianato/toxicidad , China , Hígado/metabolismo , Colestasis/inducido químicamente , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Colestasis Intrahepática/inducido químicamente , Isotiocianatos/efectos adversos , Isotiocianatos/metabolismo , Ácidos y Sales Biliares/metabolismo
13.
Sci Bull (Beijing) ; 69(5): 636-647, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38158292

RESUMEN

Lipid peroxidation (LPO), the process of membrane lipid oxidation, is a potential new form of cell death for cancer treatment. However, the radical chain reaction involved in LPO is comprised of the initiation, propagation (the slowest step), and termination stages, limiting its effectiveness in vivo. To address this limitation, we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation, thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes. Firstly, radical chain transfer agent (CTA-1)/Fe nanoparticles (CTA-Fe NPs-1) was synthesized. Notably, CTA-1 convert low activity peroxyl radicals (ROO·) into high activity alkoxyl radicals (RO·), creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation. Additionally, CTA-1/Fe ions enhance reactive oxygen species (ROS) generation, consume glutathione (GSH), and thereby inactivate GPX-4, promoting the initiation stage and reducing termination of free radical reaction. CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes, leading to highly effective treatment in cancer cells. In addition, CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging (MRI). In summary, CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation, propagation, and inhibiting termination step, promoting the cycle of free radical reaction, resulting in effective anticancer outcomes in tumor-bearing mice.


Asunto(s)
Glutatión , Neoplasias , Ratones , Animales , Peroxidación de Lípido , Oxidación-Reducción , Radicales Libres/metabolismo , Especies Reactivas de Oxígeno , Glutatión/metabolismo , Neoplasias/diagnóstico por imagen
14.
Dent Traumatol ; 29(2): 103-9, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22681634

RESUMEN

BACKGROUND: Periodontal tissue regeneration presents a highly promising method for restoring periodontal structures. The development of a suitable bioactive scaffold that promotes cell proliferation and differentiation is critical in periodontal tissue engineering. The aim of this study was to evaluate the biocompatibility of a novel 3-dimensional hydroxyapatite-collagen scaffold with human periodontal ligament (hPDL) cell culture. METHODS: The scaffold was produced from a natural collagen matrix - purified porcine acellular dermal matrix (PADM), which was then treated with hydroxyapatite (HA) through a biomimetic chemical process to obtain hydroxyapatite-porcine acellular dermal matrix (HA-PADM) scaffold. The hPDL cells were cultured with HA-PADM scaffolds for 1, 3, 6, 14, and 28 days. The cell viability assay, scanning electron microscopy (SEM), hematoxylin and eosin (H&E) staining, immunohistochemistry, and confocal microscopy were employed in different time points to evaluate the biocompatibility of the scaffolds with hPDL cells. RESULTS: The cell viability assay (WST-1 test) verified cell proliferation on the HA-PADM scaffolds. The SEM study showed unique morphology of hPDL cells, which attach and spread on the surface of the scaffolds. The H&E staining, immunohistochemistry, and confocal microscopy demonstrated that hPDL cells were able to grow into the HA-PADM scaffolds and maintain viability after prolonged culture. CONCLUSIONS: This study proved that HA-PADM scaffold is -biocompatible for hPDL cells. The cells were able to proliferate and migrate into the scaffold. These observations suggest that HA-PADM is a potential cell carrier for periodontal tissue regeneration.


Asunto(s)
Dermis Acelular/metabolismo , Colágeno , Durapatita , Ligamento Periodontal/citología , Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Materiales Biocompatibles , Técnicas de Cultivo de Célula , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Humanos , Inmunohistoquímica , Microscopía Electrónica de Rastreo , Ligamento Periodontal/crecimiento & desarrollo , Porcinos , Andamios del Tejido/química
15.
N Y State Dent J ; 79(2): 31-5, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23691726

RESUMEN

Permanent tooth agenesis is among the most common developmental anomalies encountered in dental practice. The purpose of this study was to investigate the prevalence and characteristics of tooth agenesis in orthodontic patients in Western New York. Compared to similar studies, it was found that the prevalence of congenitally missing permanent teeth in orthodontic patients is relatively high (11.1%) in Western New York.


Asunto(s)
Anodoncia/complicaciones , Anodoncia/epidemiología , Maloclusión/complicaciones , Femenino , Humanos , Masculino , New York/epidemiología , Prevalencia , Estudios Retrospectivos , Adulto Joven
16.
Nutrients ; 15(12)2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37375702

RESUMEN

Ancientino, a complex dietary fiber supplement mimicking the ancient diet, has improved chronic heart failure, kidney function, and constipation. However, its effect on ulcerative colitis is unknown. This study explores the impact of Ancientino on colitis caused by dextran sulfate sodium (DSS) and its mechanisms. Data analyses showed that Ancientino alleviated bodyweight loss, colon shortening and injury, and disease activity index (DAI) score, regulated levels of inflammatory factors (tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-1 beta (IL-1ß), and interleukin 6 (IL-6)), reduced intestinal permeability (d-lactate and endotoxin), fluorescein isothiocyanate-dextran (FITC-dextran), and diamine oxidase (DAO), repaired colonic function (ZO-1 and occludin), and suppressed oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA)) in vivo and in vitro. In short, this study demonstrated that Ancientino alleviates colitis and exerts an anticolitis effect by reducing inflammatory response, suppressing oxidative stress, and repairing intestinal barrier function. Thus, Ancientino may be an effective therapeutic dietary resource for ulcerative colitis.


Asunto(s)
Colitis Ulcerosa , Colitis , Animales , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Dextranos/uso terapéutico , Colitis/tratamiento farmacológico , Inflamación/metabolismo , Colon/metabolismo , Estrés Oxidativo , Interleucina-6/metabolismo , Suplementos Dietéticos , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
17.
Oncol Rep ; 50(6)2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37859622

RESUMEN

Lung squamous cell carcinoma (LSCC) is a highly heterogeneous malignancy with high mortality and few therapeutic options. Licochalcone A (LCA, PubChem ID: 5318998) is a chalcone extracted from licorice and possesses anticancer and anti­inflammatory activities. The present study aimed to elucidate the anticancer effect of LCA on LSCC and explore the conceivable molecular mechanism. MTT assay revealed that LCA significantly inhibited the proliferation of LSCC cells with less cytotoxicity towards human bronchial epithelial cells. 5­ethynyl­2'­deoxyuridine (EdU) assay demonstrated that LCA could reduce the proliferation rate of LSCC cells. The flow cytometric assays indicated that LCA increased the cell number of the G1 phase and induced the apoptosis of LSCC cells. LCA downregulated the protein expression of cyclin D1, cyclin E, CDK2 and CDK4. Meanwhile, LCA increased the expression level of Bax, cleaved poly(ADP­ribose)polymerase­1 (PARP1) and caspase 3, as well as downregulated the level of Bcl­2. Proteomics assay demonstrated that LCA exerted its antitumor effects via inhibiting mitogen­activated protein kinase (MAPK) signaling pathways and the expression of F­box protein 5 (FBXO5). Western blot analysis showed that LCA decreased the expression of p­ERK1/2, p­p38MAPK and FBXO5. In the xenograft tumors of LSCC, LCA significantly inhibited the volumes and weight of tumors in nude mice with little toxicity in vital organs. Therefore, the present study demonstrated that LCA effectively inhibited cell proliferation and induced apoptosis in vitro, and suppressed xenograft tumor growth in vivo. LCA may serve as a future therapeutic candidate of LSCC.


Asunto(s)
Carcinoma de Células Escamosas , Chalconas , Proteínas F-Box , Neoplasias Pulmonares , Animales , Humanos , Ratones , Apoptosis , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Chalconas/farmacología , Chalconas/uso terapéutico , Proteínas F-Box/metabolismo , Pulmón/patología , Ratones Desnudos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Transducción de Señal , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo
18.
Exploration (Beijing) ; 3(3): 20220002, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37933379

RESUMEN

The acidic characteristic of the tumor site is one of the most well-known features and provides a series of opportunities for cancer-specific theranostic strategies. In this regard, pH-responsive theranostic nanoplatforms that integrate diagnostic and therapeutic capabilities are highly developed. The fluidity of the tumor microenvironment (TME), with its temporal and spatial heterogeneities, makes noninvasive molecular magnetic resonance imaging (MRI) technology very desirable for imaging TME constituents and developing MRI-guided theranostic nanoplatforms for tumor-specific treatments. Therefore, various MRI-based theranostic strategies which employ assorted therapeutic modes have been drawn up for more efficient cancer therapy through the raised local concentration of therapeutic agents in pathological tissues. In this review, we summarize the pH-responsive mechanisms of organic components (including polymers, biological molecules, and organosilicas) as well as inorganic components (including metal coordination compounds, metal oxides, and metal salts) of theranostic nanoplatforms. Furthermore, we review the designs and applications of pH-responsive theranostic nanoplatforms for the diagnosis and treatment of cancer. In addition, the challenges and prospects in developing theranostic nanoplatforms with pH-responsiveness for cancer diagnosis and therapy are discussed.

19.
Foods ; 12(21)2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37959146

RESUMEN

Ultrasound has been widely used as a green and efficient non-thermal processing technique to assist with enzymatic hydrolysis. Compared with traditional enzymatic hydrolysis, ultrasonic-pretreatment-assisted enzymatic hydrolysis can significantly improve the efficiency of enzymatic hydrolysis and enhance the biological activity of substrates. At present, this technology is mainly used for the extraction of bioactive substances and the degradation of biological macromolecules. This review is focused on the mechanism of enzymatic hydrolysis assisted by ultrasonic pretreatment, including the effects of ultrasonic pretreatment on the enzyme structure, substrate structure, enzymatic hydrolysis kinetics, and thermodynamics and the effects of the ultrasonic conditions on the enzymatic hydrolysis results. The development status of ultrasonic devices and the application of ultrasonic-assisted enzymatic hydrolysis in the food industry are briefly described in this study. In the future, more attention should be paid to research on ultrasound-assisted enzymatic hydrolysis devices to promote the expansion of production and improve production efficiency.

20.
ACS Nano ; 17(10): 9529-9542, 2023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37154230

RESUMEN

Hepatic ischemia-reperfusion (I/R) injury accompanied by oxidative stress is responsible for postoperative liver dysfunction and failure of liver surgery. However, the dynamic non-invasive mapping of redox homeostasis in deep-seated liver during hepatic I/R injury remains a great challenge. Herein, inspired by the intrinsic reversibility of disulfide bond in proteins, a kind of reversible redox-responsive magnetic nanoparticles (RRMNs) is designed for reversible imaging of both oxidant and antioxidant levels (ONOO-/GSH), based on sulfhydryl coupling/cleaving reaction. We develop a facile strategy to prepare such reversible MRI nanoprobe via one-step surface modification. Owing to the significant change in size during the reversible response, the imaging sensitivity of RRMNs is greatly improved, which enables RRMNs to monitor the tiny change of oxidative stress in liver injury. Notably, such reversible MRI nanoprobe can non-invasively visualize the deep-seated liver tissue slice by slice in living mice. Moreover, this MRI nanoprobe can not only report molecular information about the degree of liver injury but also provide anatomical information about where the pathology occurred. The reversible MRI probe is promising for accurately and facilely monitoring I/R process, accessing injury degree and developing powerful strategy for precise treatment.


Asunto(s)
Hepatopatías , Daño por Reperfusión , Ratones , Animales , Hígado/metabolismo , Daño por Reperfusión/metabolismo , Hepatopatías/metabolismo , Estrés Oxidativo , Oxidación-Reducción , Imagen por Resonancia Magnética
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