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1.
Sci Rep ; 14(1): 10817, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734827

RESUMEN

We fabricated a moisture-induced power generator on a lateral field-excited quartz resonator to simultaneously measure changes in mass and voltage generation during water vapor adsorption. Circularly interdigitated gold electrodes were vacuum deposited on the top surface and used to measure changes in mass, and two symmetric semicircular gold electrodes were vacuum deposited on the bottom surface and used to measure changes in voltage generation. After coating a thin film of a mixture comprising sodium alginate, carbon black, and polyvinyl alcohol (SCP) on the top surface, an electric field was applied to create a concentration gradient of sodium ions between the interdigitated electrodes. The changes in the resonant frequency and voltage generation of the SCP-coated quartz resonator were measured simultaneously under various relative humidity conditions. The results revealed, for the first time, three distinct voltage-generation regions during moisture adsorption: (i) a region of negligible voltage generation, (ii) that of an increase in voltage generation, and (iii) that of a decrease in voltage generation.

2.
iScience ; 27(6): 109848, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770142

RESUMEN

We have developed an eco-friendly and efficient method for hydrovoltaic power generation through carbonizing natural kelp, a hydrogel with abundant cations. Under ambient conditions, a CO2 laser beam was focused on the top surface of dried kelp, photothermally converting it into porous graphitic carbon (PGC) and reducing dissociable cations by thermal evaporation. Owing to the preservation of the bottom surface, this photothermal process yielded a PGC-hydrogel membrane (PHM) featuring a cation concentration gradient. With the introduction of deionized water to the intact region, the kelp hydrogel retained a considerable volume of water, creating a moist environment for the PGC. The cation concentration gradient facilitated a continuous migration of cations between the PGC and unaltered kelp, generating a voltage of 0.34 V and a current density of 49 µA/cm2. We demonstrated its practical applicability by turning on three light-emitting diodes using an array of eight PHMs.

3.
Neuron ; 112(8): 1200-1202, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38636452

RESUMEN

In this issue of Neuron, Yamada et al.1 show that fast excitatory neurotransmission by protons acting at acid-sensing ion channels (ASICs) mediates mechanical force-evoked signaling at the Merkel cell-neurite complex, contributing to mammalian tactile discrimination.


Asunto(s)
Células de Merkel , Neuronas , Animales , Neuronas/metabolismo , Protones , Neuritas/metabolismo , Transmisión Sináptica , Canales Iónicos Sensibles al Ácido/metabolismo , Mamíferos/metabolismo
4.
J Neurosci ; 44(15)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38471780

RESUMEN

Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hindpaw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur. Following initial loss of cutaneous afferents in the tibial nerve territory, we observed progressive centripetal reinnervation by multiple subtypes of neighboring uninjured fibers into denervated glabrous and hairy plantar skin of male mice. In addition to dermal reinnervation, CGRP-expressing peptidergic fibers slowly but continuously repopulated denervated epidermis, Interestingly, GFRα2-expressing nonpeptidergic fibers exhibited a transient burst of epidermal reinnervation, followed by a trend towards regression. Presumptive sympathetic nerve fibers also sprouted into denervated territory, as did a population of myelinated TrkC lineage fibers, though the latter did so inefficiently. Conversely, rapidly adapting Aß fiber and C fiber low threshold mechanoreceptor (LTMR) subtypes failed to exhibit convincing sprouting up to 8 weeks after nerve injury in males or females. Optogenetics and behavioral assays in male mice further demonstrated the functionality of collaterally sprouted fibers in hairy plantar skin with restoration of punctate mechanosensation without hypersensitivity. Our findings advance understanding of differential collateral sprouting among sensory neuron subpopulations and may guide strategies to promote the progression of sensory recovery or limit maladaptive sensory phenomena after peripheral nerve injury.


Asunto(s)
Traumatismos de los Nervios Periféricos , Femenino , Ratones , Masculino , Animales , Regeneración Nerviosa/fisiología , Piel/inervación , Neurogénesis , Neuronas Aferentes/fisiología
5.
ACS Appl Mater Interfaces ; 16(12): 15032-15042, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38491936

RESUMEN

Nanodevice oscillators (nano-oscillators) have received considerable attention to implement in neuromorphic computing as hardware because they can significantly improve the device integration density and energy efficiency compared to complementary metal oxide semiconductor circuit-based oscillators. This work demonstrates vertically stackable nano-oscillators using an ovonic threshold switch (OTS) for high-density neuromorphic hardware. A vertically stackable Ge0.6Se0.4 OTS-oscillator (VOTS-OSC) is fabricated with a vertical crossbar array structure by growing Ge0.6Se0.4 film conformally on a contact hole structure using atomic layer deposition. The VOTS-OSC can be vertically integrated onto peripheral circuits without causing thermal damage because the fabrication temperature is <400 °C. The fabricated device exhibits oscillation characteristics, which can serve as leaky integrate-and-fire neurons in spiking neural networks (SNNs) and coupled oscillators in oscillatory neural networks (ONNs). For practical applications, pattern recognition and vertex coloring are demonstrated with SNNs and ONNs, respectively, using semiempirical simulations. This structure increases the oscillator integration density significantly, enabling complex tasks with a large number of oscillators. Moreover, it can enhance the computational speed of neural networks due to its rapid switching speed.

6.
J Craniofac Surg ; 35(1): 133-136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37973054

RESUMEN

OBJECTIVES: This study aimed to evaluate the diagnostic performance of a deep convolutional neural network (DCNN)-based computer-assisted diagnosis (CAD) system to detect facial asymmetry on posteroanterior (PA) cephalograms and compare the results of the DCNN with those made by the orthodontist. MATERIALS AND METHODS: PA cephalograms of 1020 patients with orthodontics were used to train the DCNN-based CAD systems for autoassessment of facial asymmetry, the degree of menton deviation, and the coordinates of its regarding landmarks. Twenty-five PA cephalograms were used to test the performance of the DCNN in analyzing facial asymmetry. The diagnostic performance of the DCNN-based CAD system was assessed using independent t -tests and Bland-Altman plots. RESULTS: Comparison between the DCNN-based CAD system and conventional analysis confirmed no significant differences. Bland-Altman plots showed good agreement for all the measurements. CONCLUSIONS: The DCNN-based CAD system might offer a clinically acceptable diagnostic evaluation of facial asymmetry on PA cephalograms.


Asunto(s)
Aprendizaje Profundo , Humanos , Asimetría Facial/diagnóstico por imagen , Redes Neurales de la Computación , Algoritmos , Diagnóstico por Computador/métodos
7.
Exp Mol Med ; 55(10): 2238-2247, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37779146

RESUMEN

Histone acetylation involves the transfer of two-carbon units to the nucleus that are embedded in low-concentration metabolites. We found that lactate, a high-concentration metabolic byproduct, can be a major carbon source for histone acetylation through oxidation-dependent metabolism. Both in cells and in purified nuclei, 13C3-lactate carbons are incorporated into histone H4 (maximum incorporation: ~60%). In the purified nucleus, this process depends on nucleus-localized lactate dehydrogenase (LDHA), knockout (KO) of which abrogates incorporation. Heterologous expression of nucleus-localized LDHA reverses the KO effect. Lactate itself increases histone acetylation, whereas inhibition of LDHA reduces acetylation. In vitro and in vivo settings exhibit different lactate incorporation patterns, suggesting an influence on the microenvironment. Higher nuclear LDHA localization is observed in pancreatic cancer than in normal tissues, showing disease relevance. Overall, lactate and nuclear LDHA can be major structural and regulatory players in the metabolism-epigenetics axis controlled by the cell's own status or the environmental status.


Asunto(s)
Histonas , Ácido Láctico , Histonas/metabolismo , Ácido Láctico/metabolismo , Acetilación , L-Lactato Deshidrogenasa/genética , L-Lactato Deshidrogenasa/metabolismo , Epigénesis Genética
8.
ACS Appl Mater Interfaces ; 15(43): 50126-50133, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37852215

RESUMEN

We developed a novel hydrovoltaic power generator (HPG) using a Janus bilayer membrane with an asymmetric wettability. The Janus bilayer membrane was fabricated by stacking a hydrophobic graphene oxide (GO)-cellulose nanofiber (CNF) composite layer on a hydrophilic GO-CNF composite layer. Water supplied through the hydrophilic layer stops at the surface of the hydrophobic layer, producing separate wet and dry regions within the thin bilayer. Protons and sodium ions dissociate from oxygen-containing functional groups in the hydrophilic GO-CNF layer and migrate toward the hydrophobic layer, resulting in a maximum output voltage and current of 0.35 V and 20 µA, respectively, in deionized (DI) water. By replacement of DI water with a 0.6 M NaCl solution (i.e., the concentration of seawater), the output voltage and current were further increased to 0.55 V and 60 µA, respectively. This performance was consistent not only under low humidity due to the water supply but also under high humidity, where evaporation was restricted, indicating humidity-independent performance. The asymmetric wettability of the membrane remained stable throughout the experiment (7 days), enabling continuous power generation.

9.
Sci Rep ; 13(1): 14311, 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37652972

RESUMEN

We developed a facile method to produce a uniform chromate conversion (CC) coating on zinc alloy-plated steel substrates (ZS). When an acidic CC solution is applied to ZS (C-ZS), zinc is dissolved and chromium ions are reduced to form a chromate coating. In localized areas where zinc is excessively dissolved, zinc hydroxide particles are formed, which hinders the formation of a uniform chromate film, leaving the areas vulnerable to further corrosion (i.e., the formation of dark spots) when exposed to high humidity conditions. To suppress the excessive dissolution of zinc, the ZS surface was pretreated with thiolated polyethylene oxide to form a hydrophilic self-assembled monolayer. A more uniform protective CC coating was obtained on the pretreated ZS, resulting in superior corrosion resistance under high humidity conditions.

10.
iScience ; 26(6): 106926, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37378321

RESUMEN

Bulk evaporation of brine is a sustainable method to obtain minerals with the inherent advantage of selective crystallization based on ion solubility differences, but it has a critical drawback of requiring a prolonged time period. In contrast, solar crystallizers based on interfacial evaporation can reduce the processing time, but their ion-selectivity may be limited due to insufficient re-dissolution and crystallization processes. This study presents the first-ever development of an ion-selective solar crystallizer featuring an asymmetrically corrugated structure (A-SC). The asymmetric mountain structure of A-SC creates V-shaped rivulets that facilitate solution transport, promoting not only evaporation but also the re-dissolution of salt formed on the mountain peaks. When A-SC was employed to evaporate a solution containing a mixture of Na+ and K+ ions, the evaporation rate was 1.51 kg/m2h and the relative concentration of Na+ to K+ in the crystallized salt was 4.45 times higher than that in the initial solution.

11.
J Nanobiotechnology ; 21(1): 82, 2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36894943

RESUMEN

BACKGROUND: Glycol chitosan nanoparticles (CNPs) have emerged as an effective drug delivery system for cancer diagnosis and treatment. Although they have great biocompatibility owing to biodegradable chemical structure and low immunogenicity, sufficient information on in vivo toxicity to understand the potential risks depending on the repeated high-dose have not been adequately studied. Herein, we report the results of in vivo toxicity evaluation for CNPs focused on the number and dose of administration in healthy mice to provide a toxicological guideline for a better clinical application of CNPs. RESULTS: The CNPs were prepared by conjugating hydrophilic glycol chitosan with hydrophobic 5ß-cholanic acid and the amphiphilic glycol chitosan-5ß-cholanic acid formed self-assembled nanoparticles with its concentration-dependent homogeneous size distributions (265.36-288.3 nm) in aqueous condition. In cell cultured system, they showed significantly high cellular uptake in breast cancer cells (4T1) and cardiomyocytes (H9C2) than in fibroblasts (L929) and macrophages (Raw264.7) in a dose- and time-dependent manners, resulting in severe necrotic cell death in H9C2 at a clinically relevant highly concentrated condition. In particular, when the high-dose (90 mg/kg) of CNPs were intravenously injected into the healthy mice, considerable amount was non-specifically accumulated in major organs (liver, lung, spleen, kidney and heart) after 6 h of injection and sustainably retained for 72 h. Finally, repeated high-dose of CNPs (90 mg/kg, three times) induced severe cardiotoxicity accompanying inflammatory responses, tissue damages, fibrotic changes and organ dysfunction. CONCLUSIONS: This study demonstrates that repeated high-dose CNPs induce severe cardiotoxicity in vivo. Through the series of toxicological assessments in the healthy mice, this study provides a toxicological guideline that may expedite the application of CNPs in the clinical settings.


Asunto(s)
Quitosano , Nanopartículas , Neoplasias , Ratones , Animales , Cardiotoxicidad/etiología , Sistemas de Liberación de Medicamentos , Quitosano/toxicidad , Quitosano/química , Nanopartículas/química
12.
Biomater Res ; 26(1): 56, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36258234

RESUMEN

BACKGROUND: Photodynamic therapy (PDT) is a promising strategy to promote antitumor immunity by inducing immunogenic cell death (ICD) in tumor cells. However, practical PDT uses an intense visible light owing to the shallow penetration depth of the light, resulting in immunosuppression at the tumor tissues. METHODS: Herein, we propose an implantable micro-scale light-emitting diode device (micro-LED) guided PDT that enables the on-demand light activation of photosensitizers deep in the body to potentiate antitumor immunity with mild visible light. RESULTS: The micro-LED is prepared by stacking one to four micro-scale LEDs (100 µm) on a needle-shape photonic device, which can be directly implanted into the core part of the tumor tissue. The photonic device with four LEDs efficiently elicits sufficient light output powers without thermal degradation and promotes reactive oxygen species (ROS) from a photosensitizer (verteporfin; VPF). After the intravenous injection of VPF in colon tumor-bearing mice, the tumor tissues are irradiated with optimal light intensity using an implanted micro-LED. While tumor tissues under intense visible light causes immunosuppression by severe inflammatory responses and regulatory T cell activation, mild visible light elicits potent ICD in tumor cells, which promotes dendritic cell (DC) maturation and T cell activation. The enhanced therapeutic efficacy and antitumor immunity by micro-LED guided PDT with mild visible light are assessed in colon tumor models. Finally, micro-LED guided PDT in combination with immune checkpoint blockade leads to 100% complete tumor regression and also establishes systemic immunological memory to prevent the recurrence of tumors. CONCLUSION: Collectively, this study demonstrates that micro-LED guided PDT with mild visible light is a promising strategy for cancer immunotherapy.

13.
Adv Mater ; 34(50): e2207143, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36271720

RESUMEN

Atomic layer deposition (ALD) of Sb2 Te3 /GeTe superlattice (SL) film on planar and vertical sidewall areas containing TiN metal and SiO2 insulator is demonstrated. The peculiar chemical affinity of the ALD precursor to the substrate surface and the 2D nature of the Sb2 Te3 enable the growth of an in situ crystallized SL film with a preferred orientation. The SL film shows a reduced reset current of ≈1/7 of the randomly oriented Ge2 Sb2 Te5 alloy. The reset switching is induced by the transition from the SL to the (111)-oriented face-centered-cubic (FCC) Ge2 Sb2 Te5 alloy and subsequent melt-quenching-free amorphization. The in-plane compressive stress, induced by the SL-to-FCC structural transition, enhances the electromigration of Ge along the [111] direction of FCC structure, which enables such a significant improvement. Set operation switches the amorphous to the (111)-oriented FCC structure.

14.
ACS Appl Mater Interfaces ; 14(40): 45289-45295, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36173290

RESUMEN

We developed a novel method based on the photofragmentation of inorganic salt particles for improving the moisture-electric energy transformation performance of a moisture-driven power generator (MPG). Infrared laser irradiation on cellulose nanofiber films (CNFs) prepared by a TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation of bleached pulp induced a photothermal conversion of CNFs to porous graphitic carbon films (GCFs) with the catalyst-derived Na2O2 particles. Since the laser beam was focused on the top surface of CNF, the gradients of the photothermal conversion of CNFs and Na2O2 concentration were created along the thickness direction. Subsequent irradiation with ultraviolet (UV) light induced the photofragmentation of the micrometer-sized Na2O2 particles into smaller ones, which increased the surface area of the salt particles in contact with the GCFs and consequently increased the number of effective dissociable charge carriers. When the GCF was exposed to moisture, the dissociated sodium ions migrated along the preformed concentration gradient, producing continuous outputs of current and voltage. At 90% relative humidity, the maximum voltage and current density outputs of the MPG increased from 0.91 V and 18.7 µA/cm2 before UV irradiation to 1.10 V and 56.2 µA/cm2 after UV irradiation, respectively. Additionally, we demonstrated that a green light-emitting diode could be turned on without capacitors or rectifiers during normal breathing while wearing a face mask with three GCF arrays attached (each 3 mm × 3 mm × 0.1 mm in size).

15.
J Control Release ; 351: 37-49, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36089170

RESUMEN

Many preclinically tested nanoparticles in existing animal models fail to be directly translated into clinical applications because of their poor resemblance to human cancer. Herein, the enhanced permeation and retention (EPR) effect of glycol chitosan nanoparticles (CNPs) in different tumor microenvironments (TMEs) was compared using different pancreatic tumor models, including pancreatic cancer cell line (BxPC3), patient-derived cancer cell (PDC), and patient-derived xenograft (PDX) models. CNPs were intravenously injected into different tumor models, and their accumulation efficiency was evaluated using non-invasive near-infrared fluorescence (NIRF) imaging. In particular, differences in angiogenic vessel density, collagen matrix, and hyaluronic acid content in tumor tissues of the BxPC3, PDC, and PDX models greatly affected the tumor-targeting efficiency of CNPs. In addition, different PDX models were established using different tumor tissues of patients to predict the clinical EPR effect of CNPs in inter-patient TMEs, wherein the gene expression levels of PECAM1, COL4A1, and HAS1 in human tumor tissues were observed to be closely related to the EPR effect of CNPs in PDX models. The results suggested that the PDX models could mimic inter-patient TMEs with different blood vessel structures and extracellular matrix (ECM) content that critically affect the tumor-targeting ability of CNPs in different pancreatic PDX models. This study provides a better understanding of the heterogeneity and complexity of inter-patient TMEs that can predict the response of various nanoparticles in individual tumors for personalized cancer therapy.


Asunto(s)
Nanopartículas , Neoplasias , Animales , Humanos , Xenoinjertos , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Microambiente Tumoral , Matriz Extracelular/metabolismo , Modelos Animales de Enfermedad , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Pharmaceutics ; 14(3)2022 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-35335852

RESUMEN

Immunogenic cell death (ICD) is a powerful trigger eliciting strong immune responses against tumors. However, traditional chemoimmunotherapy (CIT) does not last long enough to induce sufficient ICD, and also does not guarantee the safety of chemotherapeutics. To overcome the disadvantages of the conventional approach, we used doxorubicin (DOX) as an ICD inducer, and poly(lactic-co-glycolic acid) (PLGA)-based nanomedicine platform for controlled release of DOX. The diameter of 138.7 nm of DOX-loaded PLGA nanoparticles (DP-NPs) were stable for 14 days in phosphate-buffered saline (PBS, pH 7.4) at 37 °C. Furthermore, DOX was continuously released for 14 days, successfully inducing ICD and reducing cell viability in vitro. Directly injected DP-NPs enabled the remaining of DOX in the tumor site for 14 days. In addition, repeated local treatment of DP-NPs actually lasted long enough to maintain the enhanced antitumor immunity, leading to increased tumor growth inhibition with minimal toxicities. Notably, DP-NPs treated tumor tissues showed significantly increased maturated dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) population, showing enhanced antitumor immune responses. Finally, the therapeutic efficacy of DP-NPs was maximized in combination with an anti-programmed death-ligand 1 (PD-L1) antibody (Ab). Therefore, we expect therapeutic efficacies of cancer CIT can be maximized by the combination of DP-NPs with immune checkpoint blockade (ICB) by achieving proper therapeutic window and continuously inducing ICD, with minimal toxicities.

17.
Nat Commun ; 13(1): 899, 2022 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-35173161

RESUMEN

Hexokinase 2 (HK2), which catalyzes the first committed step in glucose metabolism, is induced in cancer cells. HK2's role in tumorigenesis has been attributed to its glucose kinase activity. Here, we describe a kinase independent HK2 activity, which contributes to metastasis. HK2 binds and sequesters glycogen synthase kinase 3 (GSK3) and acts as a scaffold forming a ternary complex with the regulatory subunit of protein kinase A (PRKAR1a) and GSK3ß to facilitate GSK3ß phosphorylation and inhibition by PKA. Thus, HK2 functions as an A-kinase anchoring protein (AKAP). Phosphorylation by GSK3ß targets proteins for degradation. Consistently, HK2 increases the level and stability of GSK3 targets, MCL1, NRF2, and particularly SNAIL. In addition to GSK3 inhibition, HK2 kinase activity mediates SNAIL glycosylation, which prohibits its phosphorylation by GSK3. Finally, in mouse models of breast cancer metastasis, HK2 deficiency decreases SNAIL protein levels and inhibits SNAIL-mediated epithelial mesenchymal transition and metastasis.


Asunto(s)
Glucosa/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hexoquinasa/metabolismo , Neoplasias/patología , Proteínas de Anclaje a la Quinasa A/metabolismo , Células A549 , Animales , Células CHO , Carcinogénesis/patología , Línea Celular Tumoral , Cricetulus , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico/metabolismo , Desoxiglucosa/farmacología , Transición Epitelial-Mesenquimal/fisiología , Femenino , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Glicosilación , Células HCT116 , Células HEK293 , Hexoquinasa/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Metástasis de la Neoplasia/patología , Fosforilación/efectos de los fármacos , Ratas , Factores de Transcripción de la Familia Snail/metabolismo
18.
Pain ; 163(8): 1497-1510, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34784311

RESUMEN

ABSTRACT: Chronic joint pain is a major symptom in rheumatoid arthritis (RA) and its adequate treatment represents an unmet medical need. Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of RA as negative regulators of specific target mRNAs. Yet, their significance in RA pain is still not well defined. We and other groups recently identified neuronally expressed FcγRI as a key driver of arthritis pain in mouse RA models. Thus, we tested the hypothesis that miRNAs that target and regulate neuronal FcγRI attenuate RA pain. Here, we show that miR-544-3p was robustly downregulated, whereas FcγRI was significantly upregulated in the dorsal root ganglion (DRG) in mouse RA models. Intrathecal injection of miR-544-3p mimic attenuated established mechanical and heat hyperalgesia partly through the downregulation of FcγRI in the DRG in a mouse model of collagen II-induced arthritis. Moreover, this effect was likely mediated, at least in part, by FcγRI because miR-544-3p mimic downregulated Fcgr1 mRNA expression in the DRG during arthritis and genetic deletion of Fcgr1 produced similar antihyperalgesic effects in the collagen II-induced arthritis model. This notion was further supported by a dual luciferase assay showing that miR-544-3p directly targeted Fcgr1 3'UTR. In naïve mice, miR-544-3p mediated acute joint pain hypersensitivity induced by IgG immune complex through the regulation of FcγRI. These findings suggest that miR-544-3p causally participates in the maintenance of arthritis pain by targeting neuronal FcγRI, and thus define miR-544-3p as a new potential therapeutic target for treating RA pain.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , MicroARNs , Receptores de IgG , Animales , Artralgia , Artritis Experimental/genética , Artritis Reumatoide/complicaciones , Artritis Reumatoide/genética , Colágeno , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Dolor/genética , Receptores de IgG/genética , Receptores de IgG/metabolismo
19.
Biomaterials ; 279: 121189, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34695659

RESUMEN

Intraperitoneal (IP) chemotherapy has shown promising efficacy in ovarian cancer with peritoneal carcinomatosis (PC), but in vivo rapid clearance and severe toxicity of free anticancer drugs hinder the effective treatment. Herein, we propose the safe and effective IP chemotherapy with cathepsin B-specific doxorubicin prodrug nanoparticles (PNPs) in ovarian cancer with PC. The PNPs are prepared by self-assembling cathepsin B-specific cleavable peptide (FRRG) and doxorubicin (DOX) conjugates, which are further formulated with pluronic F68. The PNPs exhibit stable spherical structure and cytotoxic DOX is specifically released from PNPs via sequential enzymatic degradation by cathepsin B and intracellular proteases. The PNPs induce cytotoxicity in cathepsin B-overexpressing ovarian (SKOV-3 and HeyA8) and colon (MC38 and CT26) cancer cells, but not in cathepsin B-deficient normal cells in cultured condition. With enhanced cancer-specificity and in vivo residence time, IP injected PNPs efficiently accumulate within PC through two targeting mechanisms of direct penetration (circulation independent) and systemic blood vessel-associated accumulation (circulation dependent). As a result, IP chemotherapy with PNPs efficiently inhibit tumor progression with minimal side effects in peritoneal human ovarian tumor-bearing xenograft (POX) and patient derived xenograft (PDX) models. These results demonstrate that PNPs effectively inhibit progression of ovarian cancer with peritoneal carcinomatosis with minimal local and systemic toxicities by high cancer-specificity and favorable in vivo PK/PD profiles enhancing PC accumulation.


Asunto(s)
Nanopartículas , Neoplasias Ováricas , Neoplasias Peritoneales , Profármacos , Catepsina B , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico
20.
Anal Chem ; 93(36): 12237-12242, 2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34474555

RESUMEN

Herein, we developed a novel method for the efficient capture of waterborne bacteria by creating an autonomous internal reflux of the magnetic nanoparticle chains (MNCs) inside a flow channel. A glass tube containing positively charged polyethyleneimine-coated MNCs (PEI-MNCs) was placed at the center of a Halbach ring, generating a strong and uniform magnetic field inside the ring. When a bacteria-spiked solution was injected into the tube, the target bacteria bound to the PEI-MNCs via an electrostatic interaction remained in the tube, whereas the unbound bacteria left the tube. Some PEI-MNC-bacteria complexes left the glass tube at high flow rates because of the drag force, which reduced the capture efficiency of the device. The loss of the PEI-MNC-bacteria complexes at high flow rates was suppressed by placing a k0 ring behind the Halbach ring. The k0 ring was used to apply a magnetic force in the opposite direction of the solution flow and create an autonomous reflux of the PEI-MNCs inside the glass tube, reducing their loss and increasing their capture efficiency. The capture efficiency of Escherichia coli O157 was determined based on the cell count to be greater than 90% at a flow rate of 15 mL/min. E. coli O157 was detected using quantitative polymerase chain reaction, and the limits of detection were 2 and 3 cfu/mL in deionized water and river water, respectively.


Asunto(s)
Escherichia coli O157 , Nanopartículas de Magnetita , Bacterias , Magnetismo , Polietileneimina
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