Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 170
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Gastroenterology ; 167(2): 343-356, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38342194

RESUMEN

BACKGROUND & AIMS: Apoptosis generates plenty of membrane-bound nanovesicles, the apoptotic vesicles (apoVs), which show promise for biomedical applications. The liver serves as a significant organ for apoptotic material removal. Whether and how the liver metabolizes apoptotic vesicular products and contributes to liver health and disease is unrecognized. METHODS: apoVs were labeled and traced after intravenous infusion. Apoptosis-deficient mice by Fas mutant (Fasmut) and Caspase-3 knockout (Casp3-/-) were used with apoV replenishment to evaluate the physiological apoV function. Combinations of morphologic, biochemical, cellular, and molecular assays were applied to assess the liver while hepatocyte analysis was performed. Partial hepatectomy and acetaminophen liver failure models were established to investigate liver regeneration and disease recovery. RESULTS: We discovered that the liver is a major metabolic organ of circulatory apoVs, in which apoVs undergo endocytosis by hepatocytes via a sugar recognition system. Moreover, apoVs play an indispensable role to counteract hepatocellular injury and liver impairment in apoptosis-deficient mice upon replenishment. Surprisingly, apoVs form a chimeric organelle complex with the hepatocyte Golgi apparatus through the soluble N-ethylmaleimide-sensitive factor attachment protein receptor machinery, which preserves Golgi integrity, promotes microtubule acetylation by regulating α-tubulin N-acetyltransferase 1, and consequently facilitates hepatocyte cytokinesis for liver recovery. The assembly of the apoV-Golgi complex is further revealed to contribute to liver homeostasis, regeneration, and protection against acute liver failure. CONCLUSIONS: These findings establish a previously unrecognized functional and mechanistic framework that apoptosis through vesicular metabolism safeguards liver homeostasis and regeneration, which holds promise for hepatic disease therapeutics.


Asunto(s)
Apoptosis , Hepatocitos , Homeostasis , Regeneración Hepática , Hígado , Ratones Noqueados , Animales , Hepatocitos/metabolismo , Hepatocitos/patología , Hígado/metabolismo , Hígado/patología , Caspasa 3/metabolismo , Ratones , Hepatectomía , Modelos Animales de Enfermedad , Receptor fas/metabolismo , Receptor fas/genética , Aparato de Golgi/metabolismo , Endocitosis , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Ratones Endogámicos C57BL , Acetaminofén , Masculino
2.
Small ; 20(30): e2308790, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38396276

RESUMEN

Traditional lipid nanoparticles (LNPs) suffer from low drug loading capacity (DLC), weak stability, and lack of responsiveness. Conventional approaches to address these issues involve the synthesis of lipid-prodrug by incorporating responsive covalent linkers. However, such approaches often result in suboptimal sensitivity for drug release and undermine therapeutic effectiveness. Herein, the study reports a fundamentally different concept for designing lipid-like prodrugs through boron-nitrogen (B-N) coordination and dynamic covalent interaction. The 5-fluorouracil-based lipid-like prodrugs, featuring a borate ester consisting of a glycerophosphoryl choline head and a boronic acid-modified 5Fu/dodecanamine complex tail, are used to prepare pH/H2O2 cascade-responsive LNPs (5Fu-LNPs). The 5Fu-LNPs exhibit enhanced DLC and stability in a neutral physiological environment due to the B-N coordination and enhanced hydrophobicity. In tumors, acidic pH triggers the dissociation of B-N coordination to release prodrugs, which further responds to low H2O2 concentrations to release drugs, showcasing a potent pH/H2O2-cascade-responsive property. Importantly, 5Fu-LNPs demonstrate greater antitumor efficiency and lower toxicity compared to the commercial 5Fu. These results highlight 5Fu-LNPs as a safer and more effective alternative to chemotherapy. This work presents a unique LNP fabrication strategy that can overcome the limitations of conventional LNPs and broaden the range of intelligent nanomaterial preparation techniques.


Asunto(s)
Peróxido de Hidrógeno , Lípidos , Nanopartículas , Profármacos , Profármacos/química , Profármacos/farmacología , Nanopartículas/química , Concentración de Iones de Hidrógeno , Peróxido de Hidrógeno/química , Humanos , Lípidos/química , Fluorouracilo/química , Fluorouracilo/farmacología , Animales , Línea Celular Tumoral , Ratones , Antineoplásicos/química , Antineoplásicos/farmacología
3.
Small ; 20(16): e2307786, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38161248

RESUMEN

To date, transforming environmental energy into electricity through a non-mechanical way is challenging. Herein, a series of photomechaelectric (PME) polyurethanes containing azobenzene-based photoisomer units and ionic liquid-based dipole units are synthesized, and corresponding PME nanogenerators (PME-NGs) to harvest electricity are fabricated. The dependence of the output performance of PME-NGs on the structure of the polyurethane is evaluated. The results show that the UV light energy can directly transduce into alternating-current (AC) electricity by PME-NGs via a non-mechanical way. The optimal open-circuit voltage and short-circuit current of PME-NGs under UV illumination reach 17.4 V and 696 µA, respectively. After rectification, the AC electricity can be further transformed into direct-current (DC) electricity and stored in a capacitor to serve as a power system to actuate typical microelectronics. The output performance of PME-NGs is closely related to the hard segment content of the PME polyurethane and the radius of counter anions in the dipole units. Kelvin probe force microscopy is used to confirm the existence of the PME effect and the detailed mechanism about the generation of AC electricity in PME-NGs is proposed, referring to the back and forth drift of induced electrons on the two electrodes in contact with the PME polyurethanes.

4.
Glob Chang Biol ; 30(1): e17118, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38273573

RESUMEN

Climate change has had a significant impact on the seasonal transition dates of Arctic tundra ecosystems, causing diverse variations between distinct land surface classes. However, the combined effect of multiple controls as well as their individual effects on these dates remains unclear at various scales and across diverse land surface classes. Here we quantified spatiotemporal variations of three seasonal transition dates (start of spring, maximum normalized difference vegetation index (NDVImax ) day, end of fall) for five dominating land surface classes in the ice-free Greenland. Using a distributed snow model, structural equation modeling, and a random forest model, based on ground observations and remote sensing data, we assessed the indirect and direct effects of climate, snow, and terrain on seasonal transition dates. We then presented new projections of likely changes in seasonal transition dates under six future climate scenarios. The coupled climate, snow cover, and terrain conditions explained up to 61% of seasonal transition dates across different land surface classes. Snow ending day played a crucial role in the start of spring and timing of NDVImax . A warmer June and a decline in wind could advance the NDVImax day. Increased precipitation and temperature during July-August are the most important for delaying the end of fall. We projected that a 1-4.5°C increase in temperature and a 5%-20% increase in precipitation would lengthen the spring-to-fall period for all five land surface classes by 2050, thus the current order of spring-to-fall lengths for the five land surface classes could undergo notable changes. Tall shrubs and fens would have a longer spring-to-fall period under the warmest and wettest scenario, suggesting a competitive advantage for these vegetation communities. This study's results illustrate controls on seasonal transition dates and portend potential changes in vegetation composition in the Arctic under climate change.


Asunto(s)
Ecosistema , Tundra , Groenlandia , Estaciones del Año , Regiones Árticas , Nieve , Cambio Climático
5.
Glob Chang Biol ; 30(1): e17087, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38273494

RESUMEN

Increasing temperatures and winter precipitation can influence the carbon (C) exchange rates in arctic ecosystems. Feedbacks can be both positive and negative, but the net effects are unclear and expected to vary strongly across the Arctic. There is a lack of understanding of the combined effects of increased summer warming and winter precipitation on the C balance in these ecosystems. Here we assess the short-term (1-3 years) and long-term (5-8 years) effects of increased snow depth (snow fences) (on average + 70 cm) and warming (open top chambers; 1-3°C increase) and the combination in a factorial design on all key components of the daytime carbon dioxide (CO2 ) fluxes in a wide-spread heath tundra ecosystem in West Greenland. The warming treatment increased ecosystem respiration (ER) on a short- and long-term basis, while gross ecosystem photosynthesis (GEP) was only increased in the long term. Despite the difference in the timing of responses of ER and GEP to the warming treatment, the net ecosystem exchange (NEE) of CO2 was unaffected in the short term and in the long term. Although the structural equation model (SEM) indicates a direct relationship between seasonal accumulated snow depth and ER and GEP, there were no significant effects of the snow addition treatment on ER or GEP measured over the summer period. The combination of warming and snow addition turned the plots into net daytime CO2 sources during the growing season. Interestingly, despite no significant changes in air temperature during the snow-free time during the experiment, control plots as well as warming plots revealed significantly higher ER and GEP in the long term compared to the short term. This was in line with the satellite-derived time-integrated normalized difference vegetation index of the study area, suggesting that more factors than air temperature are drivers for changes in arctic tundra ecosystems.


Asunto(s)
Dióxido de Carbono , Ecosistema , Estaciones del Año , Dióxido de Carbono/química , Temperatura , Nieve , Tundra , Regiones Árticas , Suelo/química
6.
Lupus ; 33(2): 145-154, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38183242

RESUMEN

BACKGROUND: Circulating cell-free DNA (cfDNA) has been widely used as a new liquid-biopsy marker. Dysregulation of cfDNA has been found in patients with systemic lupus erythematosus (SLE). However, the detailed association between cfDNA and SLE has not been thoroughly studied. METHODS: Plasma samples were collected from 88 patients with active SLE and 39 patients with inactive SLE. The cfDNA concentration was determined, and the length and distribution of cfDNA fragments were verified. RESULTS: cfDNA concentrations were significantly higher in patients with active SLE than in patients with inactive SLE (0.4 [0.18-0.897] ng/µL vs 0.249 [0.144-0.431] ng/µL; p = .043). cfDNA fragments were enriched in the ranges of 153-198 bp and 300-599 bp. cfDNA concentrations were associated with the reduction of the anti-double-stranded DNA (dsDNA) antibodies titer (r = -0.301, p = .034). The presence of anti-U1 ribonucleoprotein (p = .012), anti-Sjogren syndrome A (p = .024), anti-dsDNA (p = .0208), and anti-nucleosome antibodies (p = .0382) might associate to the variation of cfDNA concentration. Reduced cfDNA concentration was associated with renal damage in active SLE patients (0.31 [0.11-0.73] ng/µL vs 0.65 [0.27-1.53] ng/µL; p = .009). The Active index, a combination model including cfDNA concentration and other clinical indices, had an area of 0.886 under the receiver operating characteristics curve for distinguishing active SLE. The Active index was positively correlated with the SLE disease activity index score (r = 0.6724, p < .0001). CONCLUSIONS: Through systematic stratified analysis and clinical algorithm model, this study found that plasma cfDNA concentration is closely related to SLE disease severity, which has guiding significance for the future clinical application of cfDNA in SLE.


Asunto(s)
Ácidos Nucleicos Libres de Células , Lupus Eritematoso Sistémico , Humanos , Biomarcadores , Anticuerpos Antinucleares , Nucleosomas
7.
Anal Chem ; 95(7): 3761-3768, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36757879

RESUMEN

Lanthanide nanoparticles exhibit unique photophysical properties and thus emerge as promising second near-infrared (NIR-II) optical agents. However, the limited luminescence brightness hampers their construction of activatable NIR-II probes. Herein, we report the synthesis of dye-sensitized lanthanide nanoprobes (NaGdF4:Nd/ICG; indocyanine green (ICG)) and their further development for in vivo activatable imaging of hypochlorite (ClO-). Dye sensitization using ICG not only shifts the optimal doping concentration of Nd3+ from 5 to 20 mol % but also leads to a 5-fold NIR-II enhancement relative to the ICG-free counterpart. Mechanistic studies reveal that such a luminescence enhancement of NaGdF4:Nd at high Nd3+ concentration is ascribed to an alleviated cross-relaxation effect due to the broad absorption of ICG and faster energy transfer process. Taking advantage of dye oxidation, the nanoprobes enable activatable NIR-II imaging of hypochlorous acid (ClO-) in a drug-induced lymphatic inflammation mouse model. This work thus provides a simple, yet effective luminescence enhancement strategy for constructing lanthanide nanoprobes at higher activator doping concentration toward activatable NIR-II molecular imaging.


Asunto(s)
Elementos de la Serie de los Lantanoides , Nanopartículas del Metal , Animales , Ratones , Luminiscencia , Diagnóstico por Imagen , Verde de Indocianina/farmacología
8.
Phys Chem Chem Phys ; 25(29): 20121-20127, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37462941

RESUMEN

Tuning an oxide/metal interface is of critical importance for the performance enhancement of many heterogeneous catalytic reactions. However, catalytic oxidation occurring at the interface between non-reducible oxide and metal has been challenging, since non-reducible oxides hardly lose their lattice oxygen (OL) or dissociate O2 from the gas phase. In this work, a ZnO monolayer film on Au(111) is used as an inverse catalyst to investigate CO oxidation occurring at the ZnO/Au(111) interface via high pressure scanning tunneling microscopy. Surface science experiments indicate that oxygen intercalation under the ZnO monolayer film, termed ZnO/O/Au(111), can be achieved via a surface reaction with 1 × 10-6 mbar O3. Subsequent exposure of the formed ZnO/O/Au(111) surface to mbar CO at room temperature leads to the recovery of the pristine ZnO/Au(111) surface. Theoretical calculations reveal that OL adjacent to intercalated oxygen (Oint) is activated due to the OL-Zn-Oint bonding and surface corrugation, which can be directly involved in CO oxidation. Subsequently, Oint migrates to the formed oxygen vacancy from the subsurface resuming the pristine ZnO structure. These results thus reveal that oxygen intercalation underneath single-layer ZnO will strongly boost the oxidation reaction via activating adjacent lattice oxygen atoms.

9.
Bioorg Chem ; 131: 106337, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36603244

RESUMEN

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 µM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 µM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 µM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H2S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections.


Asunto(s)
Antibacterianos , Arginina , Diseño de Fármacos , Ácido Glicirretínico , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Antibacterianos/farmacología , Arginina/biosíntesis , Escherichia coli/efectos de los fármacos , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Sulfuro de Hidrógeno/metabolismo
10.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36077484

RESUMEN

Peroxisomes are a class of simple organelles that play an important role in plant reactive oxygen species (ROS) metabolism. Experimental evidence reveals the involvement of ROS in programmed cell death (PCD) in plants. Plant PCD is crucial for the regulation of plant growth, development and environmental stress resistance. However, it is unclear whether the ROS originated from peroxisomes participated in cellular PCD. Enzymes involved in the peroxisomal ROS metabolic pathways are key mediators to figure out the relationship between peroxisome-derived ROS and PCD. Here, we summarize the peroxisomal ROS generation and scavenging pathways and explain how peroxisome-derived ROS participate in PCD based on recent progress in the functional study of enzymes related to peroxisomal ROS generation or scavenging. We aimed to elucidate the role of the peroxisomal ROS regulatory system in cellular PCD to show its potential in terms of accurate PCD regulation, which contribute to environmental stress resistance.


Asunto(s)
Apoptosis , Peroxisomas , Apoptosis/fisiología , Redes y Vías Metabólicas , Peroxisomas/metabolismo , Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
11.
Saudi Pharm J ; 30(3): 265-282, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35498223

RESUMEN

Armodafinil inclusion complex (AIC) hydrogel was prepared and evaluated for its therapeutic effect on Post-traumatic Stress Disorder (PTSD). After computer simulation and physicochemical property investigation, the AIC was formed by lyophilization of armodafinil with ethanol as solvent and hydroxypropyl-beta-cyclodextrin (HP-ß-CD) aqueous solution, in which the molar ratio of armodafinil and HP-ß-CD was 1-1. The AIC encapsulation efficiency (EE) was (90.98 ± 3.72)% and loading efficiency (LE) was (13.95 ± 0.47)% and it increased the solubility of armodafinil in aqueous solution to 21 times. AIC hydrogel was prepared by adding AIC to methylcellulose (MC) hydrogels (3.33% w/v), and its higher drug release amount and slower release rate were testified by the in-vitro release assay and the rheological test. The mucosa irritation of AIC hydrogel was also evaluated. Healthy group, Model group, Sertraline group with 30 mg/kg sertraline gavage, AIC Hydrogel group with 20 mg/kg AIC hydrogel intranasal administration and AIC Aqueous Solution group with 20 mg/kg AIC aqueous solution gavage were set up for the treatment of mice with PTSD generated from foot shock method. Based on freezing response test in fear-conditioning box and open field test, compared with other groups, PTSD mice in AIC Hydrogel group showed significant improvement in behavioral parameters after 11 days of continuous drug administration and 5 days of drug withdrawal. After sacrifice, the plasma CORT level of PTSD mice in AIC Hydrogel group was elevated compared to Model group. Besides, the western blot (WB) of hippocampal brain-derived neurotrophic factor (BDNF) and amygdala dopamine transporter (DAT) immunohistochemistry sections indicated that AIC hydrogel had a protective effect on the brain tissue of PTSD mice. The brain targeting of intranasal administration was evaluated by fluorescence imaging characteristics of Cy7 hydrogel in the nasal route of drug administration, pharmacokinetics and in-vivo distribution of armodafinil. In short, AIC hydrogel is a promising formulation for the treatment of PTSD based on its high brain delivery and anti-PTSD effect.

12.
J Am Chem Soc ; 142(14): 6822-6832, 2020 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-32196319

RESUMEN

Biocatalytic reactions in living cells involve complex transformations in the spatially confined microenvironments. Inspired by biological transformation processes, we demonstrate effective biocatalytic cascade driven photodynamic therapy in tumor-bearing mice by the integration of an artificial enzyme (ultrasmall Au nanoparticles) with upconversion nanoparticles (NaYF4@NaYb0.92F4:Er0.08@NaYF4)zirconium/iron porphyrin metal-organic framework core-shell nanoparticles (UMOF NPs) which act as biocatalysts and nanoreactors. The construction of core-shell UMOF NPs are realized by using a unique "solvent-assisted self-assembly" method. The integration of ultrasmall AuNPs on the UMOFs matrix leads to glucose depletion, providing Au-mediated cancer therapy via glucose oxidase like catalytic activity. Meanwhile, the UMOF matrix acts as a near-infrared (NIR) light photon-activated singlet oxygen generator through a continuous supply of oxygen via hydrogen peroxide decomposition upon irradiation. Such kinds of biocatalysts offer exciting opportunities for biomedical, catalytical ,and energy applications.


Asunto(s)
Nanopartículas del Metal/química , Estructuras Metalorgánicas/metabolismo , Fotoquimioterapia/métodos , Humanos
13.
Small ; 16(42): e2004016, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32985099

RESUMEN

Chemical transformation in cellular environment is critical for regulating biological processes and metabolic pathways. Harnessing biocatalytic cascades to produce chemicals of interest has become a research focus to benefit industrial and pharmaceutic areas. Nanoreactors, which can act as artificial cell-like devices to organize cascade reactions, have been recently proposed for potential therapeutic applications for life-threatening illnesses. Among various types of nanomaterials, there is a growing interest in 2D metal-organic frameworks (MOFs). By virtue of the ultralarge specific surface area, high porosity, and structural diversity, 2D MOF nanosheets hold great promise for a broad spectrum of biomedical use. Herein, a unique planar MOF-based hybrid architecture (GMOF-LA) is introduced by incorporating ultrasmall gold nanoparticles (Au NPs) as nanozyme and l-Arginine (l-Arg) as nitric oxide (NO) donor. The prepared Au NPs enable oxidation of glucose into hydrogen peroxide, which drives biocatalytic cascades to covert l-Arg into NO. Interestingly, the well-designed nanosheets not only possess excellent catalytical activity for NO generation, resulting in gas therapeutic effect, but also serve as a desired photosensitizer for photodynamic therapy. This study establishes a good example of exploring bioinspired nanoreactors for cooperative anticancer effect, which may pave the path for future "bench-to-bedside" design of nanomedicine.


Asunto(s)
Nanopartículas del Metal , Estructuras Metalorgánicas , Neoplasias , Catálisis , Oro , Humanos , Neoplasias/tratamiento farmacológico
14.
Fish Shellfish Immunol ; 99: 473-482, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32070785

RESUMEN

Salinity is a limiting factor for many marine organisms, including fishes. The shift in the ambient salinity can cause osmotic stress and arouse immune responses in fish. In this study, yellowfin seabream (Acanthopagrus latus), a euryhaline marine teleost, was used to investigate immune responses of different tissues (gill, liver, and muscle) under hypoosmotic stress. Comparative transcriptomic and physiological analyses of three tissues were conducted after fish exposed to the fresh water (FW, salinity = 0 ppt), low-saline water (LW, salinity = 3 ppt), and brackish water (BW, salinity = 6 ppt) for 8 days. The results showed that hypoosmotic stress dramatically altered the gene expression of three tissues in yellowfin seabream; The investigation of differentially expressed genes (DEGs) related to osmoregulation and immune response indicated that T cell-mediate immunity pathways were essential to tackle such stress. In terms of tissues, gill was found to be the most sensitive tissue under hypoosmotic stress by enhancing of Na+K+-ATPase activity and preventing the loss of Na+ and K+; Liver, on the other hand, was under the most sever oxidative stress indicated by the fluctuation of SOD, CAT activities and the MDA content; In contrast, muscle had the least osmoregulation and immune related response. We also identified several potential candidate genes, which may serve as gene indicators to identify the stressor. Overall, this study provides preliminary mechanistic insights into hypoosmotic stress adaption of aquatic organism.


Asunto(s)
Osmorregulación , Presión Osmótica , Salinidad , Dorada/genética , Dorada/inmunología , Linfocitos T/inmunología , Aclimatación , Animales , Agua Dulce , Perfilación de la Expresión Génica , Branquias/inmunología , Hígado/inmunología , Músculos/inmunología , Análisis de Secuencia de ARN
15.
Chem Soc Rev ; 48(7): 2053-2108, 2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30259015

RESUMEN

The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.


Asunto(s)
Hipertermia Inducida , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Técnicas Fotoacústicas , Fototerapia , Nanomedicina Teranóstica , Humanos
16.
Sensors (Basel) ; 20(9)2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-32365747

RESUMEN

Convolution neural network (CNN)-based detectors have shown great performance on ship detections of synthetic aperture radar (SAR) images. However, the performance of current models has not been satisfactory enough for detecting multiscale ships and small-size ones in front of complex backgrounds. To address the problem, we propose a novel SAR ship detector based on CNN, which consist of three subnetworks: the Fusion Feature Extractor Network (FFEN), Region Proposal Network (RPN), and Refine Detection Network (RDN). Instead of using a single feature map, we fuse feature maps in bottom-up and top-down ways and generate proposals from each fused feature map in FFEN. Furthermore, we further merge features generated by the region-of-interest (RoI) pooling layer in RDN. Based on the feature representation strategy, the CNN framework constructed can significantly enhance the location and semantics information for the multiscale ships, in particular for the small ships. On the other hand, the residual block is introduced to increase the network depth, through which the detection precision could be further improved. The public SAR ship dataset (SSDD) and China Gaofen-3 satellite SAR image are used to validate the proposed method. Our method shows excellent performance for detecting the multiscale and small-size ships with respect to some competitive models and exhibits high potential in practical application.

17.
J Am Chem Soc ; 141(25): 9937-9945, 2019 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-31199131

RESUMEN

Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H2O2 into hydroxyl radical (•OH), but endogenous H2O2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H2O2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2. The CP nanodots were prepared through coordination of H2O2 to Cu2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.


Asunto(s)
Antineoplásicos/uso terapéutico , Cobre/química , Peróxido de Hidrógeno/metabolismo , Neoplasias/tratamiento farmacológico , Puntos Cuánticos/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Radical Hidroxilo/metabolismo , Lisosomas/efectos de los fármacos , Ratones , Puntos Cuánticos/química , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Small ; 15(16): e1900691, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30913380

RESUMEN

Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.


Asunto(s)
Portadores de Fármacos , Fulerenos/química , Gadolinio/química , Imagen por Resonancia Magnética , Animales , Medios de Contraste/química , Preparaciones de Acción Retardada/uso terapéutico , Doxorrubicina/química , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Ratones , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Polímeros/química , Microambiente Tumoral
19.
Small ; 15(4): e1804131, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30565431

RESUMEN

During photodynamic therapy (PDT), severe hypoxia often occurs as an undesirable limitation of PDT owing to the O2 -consuming photodynamic process, compromising the effectiveness of PDT. To overcome this problem, several strategies aiming to improve tumor oxygenation are developed. Unlike these traditional approaches, an opposite method combining hypoxia-activated prodrug and PDT may provide a promising strategy for cancer synergistic therapy. In light of this, azido-/photosensitizer-terminated UiO-66 nanoscale metal-organic frameworks (UiO-66-H/N3 NMOFs) which serve as nanocarriers for the bioreductive prodrug banoxantrone (AQ4N) are engineered. Owing to the effective shielding of the nanoparticles, the stability of AQ4N is well preserved, highlighting the vital function of the nanocarriers. By virtue of strain-promoted azide-alkyne cycloaddition, the nanocarriers are further decorated with a dense PEG layer to enhance their dispersion in the physiological environment and improve their therapeutic performance. Both in vitro and in vivo studies reveal that the O2 -depleting PDT process indeed aggravates intracellular/tumor hypoxia that activates the cytotoxicity of AQ4N through a cascade process, consequently achieving PDT-induced and hypoxia-activated synergistic therapy. Benefiting from the localized therapeutic effect of PDT and hypoxia-activated cytotoxicity of AQ4N, this hybrid nanomedicine exhibits enhanced therapeutic efficacy with negligible systemic toxicity, making it a promising candidate for cancer therapy.


Asunto(s)
Nanomedicina/métodos , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Microscopía Confocal , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Nanopartículas/ultraestructura , Neoplasias/metabolismo
20.
Small ; 15(41): e1903422, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31448577

RESUMEN

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv ß3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.


Asunto(s)
Gadolinio/química , Imagen por Resonancia Magnética , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Tamaño de la Partícula , Resinas Acrílicas/química , Línea Celular Tumoral , Humanos , Nanopartículas/ultraestructura
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA