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1.
Technol Health Care ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38759058

RESUMEN

BACKGROUND: Plane-wave imaging is widely employed in medical imaging due to its ultra-fast imaging speed. However, the image quality is compromised. Existing techniques to enhance image quality tend to sacrifice the imaging frame rate. OBJECTIVE: The study aims to reconstruct high-quality plane-wave images while maintaining the imaging frame rate. METHODS: The proposed method utilizes a U-Net-based generator incorporating a multi-scale convolution module in the encoder to extract information at different levels. Additionally, a Dynamic Criss-Cross Attention (DCCA) mechanism is proposed in the decoder of the U-Net-based generator to extract both local and global features of plane-wave images while avoiding interference caused by irrelevant regions. RESULTS: In the reconstruction of point targets, the experimental images achieved a reduction in Full Width at Half Maximum (FWHM) of 0.0499 mm, compared to the Coherent Plane-Wave Compounding (CPWC) method using 75-beam plane waves. For the reconstruction of cyst targets, the simulated image achieved a 3.78% improvement in Contrast Ratio (CR) compared to CPWC. CONCLUSIONS: The proposed model effectively addresses the issue of unclear lesion sites in plane-wave images.

2.
Bioact Mater ; 38: 374-383, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38770429

RESUMEN

Implant-related osteomyelitis is a formidable hurdle in the clinical setting and is characterized by inflammation, infection, and consequential bone destruction. Therefore, effective reactive oxygen species (ROS) scavenging, bacterial killing, and subsequent bone tissue repair are urgently needed for the treatment of difficult-to-heal osteomyelitis. Herein, we utilized the eddy-thermal effect of magnesium (Mg) implants under an alternating magnetic field (AMF) for the controlled release of H2 gas and ions (OH- and Mg2+) for the treatment of osteomyelitis. H2 released by Mg rods under AMFs effectively scavenged cytotoxic ROS, exhibiting anti-inflammatory effects and consequently disrupting the environment of bacterial infections. In addition, the OH- hindered the energy metabolism of bacteria by effectively neutralizing protons within the microenvironment. Moreover, H2 impaired the permeability of bacterial membranes and expedited the damage induced by OH-. This synergistic AMF-induced H2 and proton depletion treatment approach not only killed both gram-negative and gram-positive bacteria but also effectively treated bacterial infections (abscesses and osteomyelitis). Moreover, Mg2+ released from the Mg rods enhanced and accelerated the process of bone osteogenesis. Overall, our work cleverly exploited the eddy-thermal effect and chemical activity of Mg implants under AMFs, aiming to eliminate the inflammatory environment and combat bacterial infections by the simultaneous release of H2, OH-, and Mg2+, thereby facilitating tissue regeneration. This therapeutic strategy achieved multiple benefits in one, thus presenting a promising avenue for clinical application.

4.
ACS Nano ; 18(15): 10495-10508, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38556991

RESUMEN

Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer therapy. An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via the Jahn-Teller effect induced by the introduction of Cu2+, and the synthesized ZCA NSs regulated the intricate tumor microenvironment (TME) by depleting endogenous glutathione (GSH) to amplify oxidative stress for further enhanced SDT performance. Furthermore, cuproptosis was evoked by intracellular overload of Cu2+ and amplified by SDT, leading to irreversible proteotoxicity. In vitro results showed that such synergetic SDT/cuproptosis triggered immunogenic cell death (ICD) and promoted the maturation of dendritic cells (DCs). Furthermore, the as-synthesized ZCA NS-mediated SDT/cuproptosis thoroughly eradicated the in vivo solid tumors and simultaneously elicited antitumor immunity to suppress lung and liver metastasis. Overall, this work established a nanoplatform for synergistic SDT/cuproptosis with a satisfactory antitumor immunity.


Asunto(s)
Neoplasias Hepáticas , Neoplasias , Terapia por Ultrasonido , Humanos , Cobre , Electrónica , Glutatión , Hidróxidos , Neoplasias Hepáticas/tratamiento farmacológico , Inmunidad , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
5.
Technol Health Care ; 32(1): 31-53, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37781821

RESUMEN

BACKGROUND: Pulse-inversion-based tissue harmonic imaging has been utilized for many years because it can effectively eliminate the harmonic leakage and produce low side-lobe. However, the pulse inversion method is sensitive to imaging object movements, which may result in motion artifacts. Spatial resolution and contrast were limited. OBJECTIVE: To improve ultrasound image quality by a new pulse-inversion-based tissue harmonic imaging technique. METHODS: Continuous wavelet transform is applied to investigate the correlation between mother wavelet and the received echoes from two opposite pulses. To get a better correlation, a novel mother wavelet named 'tissue wavelet' is designed based on the Khokhlov-Zabolotskaya- Kuznetsov (KZK) wave equation. Radio frequency data were obtained from open Ultrasonix SonixTouch imaging system. Experiments were carried on ultrasonic tissue phantom, human carotid artery and human liver. RESULTS: The average improvement of lateral spatial resolution is 49.52% compared to pulse-inversion-based tissue second-harmonic Imaging (PIHI). Contrast ratio (CR) and contrast-to-noise ratio (CNR) increased by 5.55 dB and 1.40 dB over PIHI. Tissue wavelet performs better than Mexh and Morl wavelet in lateral spatial resolution, CR, and CNR. CONCLUSION: The proposed technique effectively improves the imaging quality in lateral spatial resolution, CR, and CNR.


Asunto(s)
Hígado , Análisis de Ondículas , Humanos , Ultrasonografía/métodos , Hígado/diagnóstico por imagen , Movimiento (Física) , Movimiento , Fantasmas de Imagen
6.
PLoS One ; 18(12): e0294993, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38127966

RESUMEN

Shale is a kind of sedimentary rock with an obvious bedding structure. The effect of the bedding plane on hydraulic fracture initiation, propagation, and complex fracture network formation is remarkable and a major problem in hydraulic fracturing and shale oil and gas development. In this study, a criterion is established to predict the evolution behavior of hydraulic fractures (HF) under different confining pressure differences and intersection angles. This criterion is intended to predict the types of interaction between HFs and bedding planes (BPs): penetrating, slipping, or dilating. The dependence of crossing on the intersection angle and the principal stress difference is quantitatively presented using the criterion. Meanwhile, 20 simulations with principal stress differences of 2, 4, 6, and 8 MPa and intersection angles of 30°, 45°, 60°, 75°, and 90° were simulated using the RFPA2D-Flow code. Simulation results exhibit good agreement with the criterion results for a wide range of angles. The investigation showed that HFs tend to penetrate BPs under high confining pressure differences and intersection angles and open BPs under low confining pressure differences and intersection angles. In addition to the above two forms, HFs slip due to shear. The criterion can provide relevant reference about the formation of complex fracture networks in shale layers.


Asunto(s)
Fracking Hidráulico , Gas Natural , Fracking Hidráulico/métodos , Minerales
7.
ACS Nano ; 17(21): 21539-21552, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37843009

RESUMEN

The occurrence and development of inflammatory bowel diseases (IBDs) are inextricably linked to the excessive production of reactive oxygen species (ROS). Thus, there is an urgent need to develop innovative tactics to combat IBDs and scavenge excess ROS from affected areas. Herein, silicon hydrogen nanoparticles (SiH NPs) with ROS-scavenging ability were prepared by etching Si nanowires (NWs) with hydrogen fluoride (HF) to alleviate the symptoms associated with IBD by orally targeting the inflamed colonic sites. The strong reductive Si-H bonds showed excellent stability in the gastric and intestinal fluids, which exhibited efficient ROS-scavenging effects to protect cells from high oxidative stress-induced death. After oral delivery, the negatively charged SiH NPs were specifically adsorbed to the positively charged inflammatory epithelial tissues of the colon for an extended period via electrostatic interactions to prolong the colonic residence time. SiH NPs exhibited significant preventive and therapeutic effects in dextran sodium sulfate-induced prophylactic and therapeutic mouse models by inhibiting colonic shortening, reducing the secretion of pro-inflammatory cytokines, regulating macrophage polarization, and protecting the colonic barrier. As determined using 16S rDNA high-throughput sequencing, the oral administration of SiH NPs treatment led to changes in the abundance of the intestinal microbiome, which improved the bacterial diversity and restored the relative abundance of beneficial bacteria after the inflamed colon. Overall, our findings highlight the broad application of SiH-based anti-inflammatory drugs in the treatment of IBD and other inflammatory diseases.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Nanoestructuras , Silicio , Animales , Ratones , Antiinflamatorios/uso terapéutico , Bacterias , Colon , Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Especies Reactivas de Oxígeno , Silicio/farmacología , Silicio/uso terapéutico
8.
Exploration (Beijing) ; 3(1): 20220041, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37323619

RESUMEN

Oxidative stress from reactive oxygen species (ROS) is a reperfusion injury factor that can lead to cell damage and death. Here, ultrasmall iron-gallic acid coordination polymer nanodots (Fe-GA CPNs) were developed as antioxidative neuroprotectors for ischemia stroke therapy guided by PET/MR imaging. As proven by the electron spin resonance spectrum, the ultrasmall Fe-GA CPNs with ultrasmall size, scavenged ROS efficiently. In vitro experiments revealed that Fe-GA CPNs could protect cell viability after being treated with hydrogen peroxide (H2O2) and displayed the effective elimination of ROS by Fe-GA CPNs, which subsequently restores oxidation balance. When analyzing the middle cerebral artery occlusion model, the neurologic damage displayed by PET/MR imaging revealed a distinct recovery after treatment with Fe-GA CPNs, which was proved by 2,3,5-triphenyl tetrazolium chloride staining. Furthermore, immunohistochemistry staining indicated that Fe-GA CPNs inhibited apoptosis through protein kinase B (Akt) restoration, whereas western blot and immunofluorescence indicated the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathway following Fe-GA CPNs application. Therefore, Fe-GA CPNs exhibit an impressive antioxidative and neuroprotective role via redox homeostasis recovery by Akt and Nrf2/HO-1 pathway activation, revealing its potential for clinical ischemia stroke treatment.

9.
Acta Pharm Sin B ; 13(4): 1726-1739, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37139421

RESUMEN

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

10.
Artículo en Inglés | MEDLINE | ID: mdl-37022068

RESUMEN

With the improvement of quality of life, people are more and more concerned about the quality of sleep. The electroencephalogram (EEG)-based sleep stage classification is a good guide for sleep quality and sleep disorders. At this stage, most automatic staging neural networks are designed by human experts, and this process is time-consuming and laborious. In this paper, we propose a novel neural architecture search (NAS) framework based on bilevel optimization approximation for EEG-based sleep stage classification. The proposed NAS architecture mainly performs the architectural search through a bilevel optimization approximation, and the model is optimized by search space approximation and search space regularization with parameters shared among cells. Finally, we evaluated the performance of the model searched by NAS on the Sleep-EDF-20, Sleep-EDF-78 and SHHS datasets with an average accuracy of 82.7%, 80.0% and 81.9%, respectively. The experimental results show that the proposed NAS algorithm provides some reference for the subsequent automatic design of networks for sleep classification.

11.
Sci Total Environ ; 875: 162542, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36870484

RESUMEN

Although high levels of geogenic ammonium in groundwater have been widely reported, the mechanisms controlling its heterogeneous distribution are not yet well understood. In this study, a comprehensive investigation of hydrogeology, sediments, and groundwater chemistry was coupled with a set of incubation experiments to reveal the contrasting mechanisms of groundwater ammonium enrichment at two adjacent monitoring sites with different hydrogeologic settings in the central Yangtze River basin. Significant differences were found in the ammonium concentrations of groundwater at two monitoring sites, with the ammonium concentrations in the Maozui (MZ) section (0.30-5.88 mg/L; average of 2.93 mg/L) being much higher than those in the Shenjiang (SJ) section (0.12-2.43 mg/L; average of 0.90 mg/L). For the SJ section, the aquifer medium had a low organic matter (OM) content and a weak mineralization capability, leading to a limited potential for geogenic ammonium release. Moreover, due to the presence of alternating silt and continuous fine sand layers (with coarse grains) above the underlying confined aquifer, the groundwater was in a relatively open environment with oxidizing conditions, which may have promoted the removal of ammonium. For the MZ section, the aquifer medium had a high OM content and a strong mineralization capability, leading to a much higher potential for geogenic ammonium release. Furthermore, due to the presence of a thick and continuous muddy clay layer (aquitard) above the underlying confined aquifer, the groundwater was in a closed environment with strong reducing conditions, which was conductive to the storage of ammonium. Larger sources of ammonium in the MZ section and greater consumption of ammonium in the SJ section contributed collectively to the significant differences in groundwater ammonium concentrations. This study identified contrasting mechanism of groundwater ammonium enrichment in different hydrogeologic settings, which can help explain the heterogeneous distribution of ammonium levels in groundwater.

12.
Bioact Mater ; 25: 73-85, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36733928

RESUMEN

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.

13.
Angew Chem Int Ed Engl ; 62(9): e202215467, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-36591974

RESUMEN

Oxygen-deficient molybdenum oxide (MoOX ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoOX -PEG exhibits efficient capability for US-triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX -PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX -PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS-STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX -PEG, the combination treatment of MoOX -triggered SDT and aCTLA-4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors.


Asunto(s)
Neoplasias , Óxidos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Molibdeno , Neoplasias/tratamiento farmacológico , Hipoxia , Oxígeno/metabolismo , Línea Celular Tumoral
14.
Ultrason Imaging ; 45(1): 3-16, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36524755

RESUMEN

Due to the advantages of non-radiation and real-time performance, ultrasound imaging is essential in medical imaging. Image quality is affected by the performance of the transducer in an ultrasound imaging system. For example, the bandwidth controls the pulse length, resulting in different axial resolutions. Therefore, a transducer with a large bandwidth helps to improve imaging quality. However, large bandwidths lead to increased system cost and sometimes a loss of sensitivity and lateral resolution in attenuating media. In this paper, a deconvolution recovery method combined with a frequency-domain filtering technique (DRF) is proposed to improve the imaging quality, especially for the axial resolution. In this method, the received low-bandwidth echo signals are converted into high-bandwidth signals, which is similar to the echo signals produced by a high-bandwidth transducer, and the imaging quality is improved. Simulation and experiment results show that, compared with Delay-and-sum (DAS) method, the DRF method improved axial resolution from 0.60 to 0.41 mm in simulation and from 0.62 to 0.47 mm in the tissue-mimicking phantom experiment. The contrast ratio performance is improved to some extent compared with the DAS in experimental and in-vivo images. Besides, the proposed method has the potential to further improve image quality by combining it with adaptive weightings, such as the minimum variance method.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Transductores , Ultrasonografía/métodos , Simulación por Computador , Fantasmas de Imagen , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos
15.
Technol Health Care ; 31(1): 217-237, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35964219

RESUMEN

BACKGROUND: A fundamental challenge in medical ultrasound imaging is to improve the resolution accurately. Adaptive beamforming is often used to improve lateral resolution, such as minimum variance (MV) and phase coherence factor (PCF). However, it is difficult to improve the axial resolution due to the limitation of the spatial pulse length (SPL) of the transmitted signal. OBJECTIVE: A deconvolution recovery method combines two adaptive weighting techniques to improve axial resolution. METHODS: A deconvolution recovery (DR) technique is used to improve axial resolution with a shorter SPL. Then, the DR is combined with MV and PCF (DR-MVPCF) to suppress the sidelobe. The influence of different transmission modes, regularization parameters, and the estimation of point spread function are discussed on the proposed algorithm. RESULTS: In simulation, DR-MVPCF improved axial resolution from 0.41 mm (0.98 λ) to 0.09 mm (0.21 λ) compared with MV-PCF. In the water bath experiment, DR-MVPCF provided improvement of axial resolution from 0.39 mm (0.93 λ) to 0.07 mm (0.17 λ) compared with MV-PCF. In-vivo data experiment, the DR-MVPCF method increased the speckle signal-to-noise ratio and visibility of the structure while the contrast ratio and contrast-noise ratio decreased. CONCLUSIONS: The proposed method can improve the axial resolution significantly.


Asunto(s)
Algoritmos , Procesamiento de Imagen Asistido por Computador , Humanos , Fantasmas de Imagen , Ultrasonografía/métodos , Simulación por Computador , Relación Señal-Ruido , Procesamiento de Imagen Asistido por Computador/métodos
16.
Biomaterials ; 291: 121904, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36403323

RESUMEN

Oxidative stress and mitochondrial damage are the main mechanisms of ischemia-reperfusion injury in ischemic stroke. Herein, cerium oxide nanoparticles with powerful free radical scavenging ability were used as carriers to load dl-3-n-butylphthalide (NBP-CeO2 NPs) for the combined treatment of ischemic stroke. NBP-CeO2 NPs could eliminate reactive oxygen species (ROS) in mouse brain microvascular endothelial cells and hippocampal neurons after oxygen-glucose deprivation/reoxygenation (OGD/R), and also save mitochondrial membrane potential, morphology, and function, thus alleviating the in vitro blood brain barrier (BBB) disruption and neuronal apoptosis. In the middle cerebral artery embolization/recanalization (MCAO/R) mouse model, the NBP-CeO2 NPs also possessed superior ROS scavenging ability, protected mitochondria, and preserved BBB integrity, thereby reducing cerebral infarction and cerebral edema and inhibiting neuroinflammation and neuronal apoptosis. The long-term neurobehavioral tests indicated that the NBP-CeO2 NPs significantly improved sensorimotor function and spatial learning ability by promoting angiogenesis after ischemic stroke. Therefore, the NBP-CeO2 NPs provided a novel therapeutic approach for ischemic stroke by combining antioxidant and neurovascular repair abilities, highlighting its wide application in ischemia-reperfusion injury.


Asunto(s)
Accidente Cerebrovascular Isquémico , Nanopartículas , Daño por Reperfusión , Animales , Ratones , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Especies Reactivas de Oxígeno , Células Endoteliales , Daño por Reperfusión/tratamiento farmacológico
17.
J Acoust Soc Am ; 152(4): 2022, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36319262

RESUMEN

A listening test was conducted with 32 participants to obtain data on emotional changes in response to three types of urban soundscape spatial sequences. By establishing a time series model, the relationship between psychoacoustic parameters of the sequence and changes in the two dimensions of emotion was determined. Results showed that psychoacoustic parameters can explain 44% and 40%-49% of the changes in the pleasantness and arousal dimensions of emotion, respectively. Roughness and fluctuation have the highest correlation with emotional changes, while loudness and articulation index have the lowest correlation with emotional changes. This research verified the lags between psychoacoustic changes in the soundscape and the associated perceived emotion. First, there was a 3-4 s lag between psychoacoustic parameters and emotional changes. Second, changes in roughness and loudness could cause synchronous changes in emotions, while other parameters could cause delayed changes in emotions. Finally, the lag of emotion had a strong and stable explanatory power for emotional changes. This research proves the effectiveness of the time series analysis technology in establishing the dynamic relationship between the acoustic parameters of soundscape sequences and the second-by-second perceived emotions and provides a new data analysis method for in-depth study of soundscape sequence perception.


Asunto(s)
Acústica , Percepción Auditiva , Humanos , Psicoacústica , Factores de Tiempo , Percepción Auditiva/fisiología , Emociones/fisiología
18.
Front Pharmacol ; 13: 952804, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36160382

RESUMEN

Background: Previous studies have suggested that proton pump inhibitors could impair the antiplatelet effect of clopidogrel. It is uncertain whether ilaprazole affects the antiplatelet effect of clopidogrel. This study aimed to determine the drug-drug interaction between ilaprazole and clopidogrel. Methods: A randomized crossover trial of 40 healthy subjects was performed. Clopidogrel was administered alone or in combination with ilaprazole for 7 days. The maximal platelet aggregation (MPA) to 5 µmol/L adenosine diphosphate was measured by light transmission aggregometry and the platelet reactivity index (PRI) was determined by vasodilator-stimulated phosphoprotein P2Y12 assay. High on-treatment platelet reactivity (HOPR) was defined as a MPA of >40%. The inhibition of platelet aggregation (IPA) and PRI in the two phases were compared between two regimens after the last dosing. Results: IPA was comparable between the two regimens at 0, 10 and 24 h (p > 0.05), but higher at 4 h in the clopidogrel alone regimen compared with that in the combined treatment regimen (75.66 ± 18.44% vs. 70.18 ± 17.67%, p = 0.031). The inhibition of PRI was comparable between the two regimens at 0 and 24 h. There were no significant differences in the area under the time-IPA% curve (AUC) or the incidence of HOPR at all time-points between the two regimens. Conclusion: In healthy subjects, ilaprazole has limited effect on the pharmacodynamics of clopidogrel and it may not be clinically relevant. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000031482].

19.
Angew Chem Int Ed Engl ; 61(39): e202208849, 2022 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-35929496

RESUMEN

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)-mediated cancer therapy. Herein, vanadium-based nanocatalysts, hydrogen vanadium bronzes (HX V2 O5 , for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi-functional catalytic activity in decomposing H2 O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS-mediated cancer therapies.


Asunto(s)
Neoplasias , Vanadio , Línea Celular Tumoral , Glutatión/metabolismo , Humanos , Hidrógeno , Neoplasias/terapia , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
20.
Bioact Mater ; 18: 569-582, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35845318

RESUMEN

Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation. The constructed RA@BSA@Cur NPs not only induced polarization of macrophages toward pro-regenerative phenotypes and markedly reduced the inflammatory response of macrophages or microglia, but also increased neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, improved the differentiation of neural stem cells (NSCs) into ß3-tubulin+ neurons, and reversed the pro-astrocyte differentiation effect of inflammatory cytokines on NSCs. In vivo experiments revealed that RA@BSA@Cur NPs regulated the phenotypic polarization of macrophages, inhibited the release of inflammatory mediators, promoted functional neuron regeneration and motor function, and further inhibited scar tissue formation. This study highlighted that the BSA-based biomimetic nanomaterials could be used as ROS scavengers and nerve regeneration promoters for treating SCI.

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