RESUMEN
Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H2O2) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO2@Au hydrogel system (CuO2@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO2@Au Gel is constructed by embedding therapeutic CuO2@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO2@Au in CuO2@Au Gel is capable of self-supplying H2O2 and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO2@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.
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Airborne total suspended particles (TSP) and particulate matter (PM2.5 ) threaten global health and their potential impact on cardiovascular and respiratory diseases are extensively studied. Recent studies attest premature deaths, low birth weight, and congenital anomalies in the fetus of pregnant women exposed to air pollution. In this regard, only few studies have explored the effects of TSP and PM2.5 on cardiovascular and cerebrovascular development. As both TSP and PM2.5 differ in size and composition, this study is attempted to assess the variability in toxicity effects between TSP and PM2.5 on the development of cardiovascular and cerebrovascular systems and the underlying mechanisms in a zebrafish model. To explore the potential toxic effects of TSP and PM2.5 , zebrafish embryos/larvae were exposed to 25, 50, 100, 200, and 400 µg/ml of TSP and PM2.5 from 24 to 120 hpf (hours post-fertilization). Both TSP and PM2.5 exposure increased the rate of mortality, malformations, and oxidative stress, whereas locomotor behavior, heart rate, blood flow velocity, development of cardiovasculature and neurovasculature, and dopaminergic neurons were reduced. The expression of genes involved in endoplasmic reticulum stress (ERS), Wnt signaling, and central nervous system (CNS) development were altered in a dose- and time-dependent manner. This study provides evidence for acute exposure to TSP and PM2.5 -induced cardiovascular and neurodevelopmental toxicity, attributed to enhanced oxidative stress and aberrant gene expression. Comparatively, the effects of PM2.5 were more pronounced than TSP.
Asunto(s)
Contaminación del Aire , Material Particulado , Contaminación del Aire/efectos adversos , Animales , Embrión no Mamífero , Femenino , Corazón , Humanos , Larva/metabolismo , Material Particulado/toxicidad , Embarazo , Pez Cebra/metabolismoRESUMEN
Particulate matter with 10⯵m or less in diameter (PM10) exposure is a major threat to health and environment around the world. Even though a number of clinical and experimental studies have focused on the cardiopulmonary effects of PM10, its impact on neurovascular development and the underlying toxicity is relatively less studied. The present study is therefore undertaken to evaluate the potential toxic effects of PM10 on neurodevelopment and the associated gene expression profiles in the zebrafish embryo/larvae. During 2017-2018, PM10 samples (24â¯h sampling, 180 sampling days) were collected in an urban downtown site of Jinan, Shandong province, China. To delineate the potential toxic effects of PM10 during neurodevelopment, zebrafish embryos/larvae were exposed to different concentrations viz., 25, 50, 100, 200, and 400⯵g/mL of PM10 solution for 24-120â¯h post-fertilization (hpf) and the effects on the mortality, morphology, swimming behavior, electroencephalogram discharges, growth of dopaminergic neurons, neurovasculature development and gene expression profiles of dopaminergic and neurodevelopment-related genes using qRT-PCR were studied. A significant increase in the mortality rate and morphological abnormalities were observed in 200⯵g/mL of the PM10 treated group at 120â¯hpf. High concentrations (≥100⯵g/mL) of PM10 exposure reduced locomotor behavior, caused abnormal electroencephalogram discharges, degeneration of dopaminergic neurons, inhibition of neurovascular development, cerebral hemorrhage, and significant changes in the expression pattern of genes involved in dopaminergic pathway and neurodevelopment such as (th1, dat, drd1, drd2a, drd3, drd4b, syn2a, gap43, α1-tubulin, gfap, map2, elavl3, eno2, neurog1, sox2, shha, and mbp). Taken together, all these parameters collectively imply developmental neurotoxicity and dysfunction of the dopaminergic neurons which provides the first evidence of PM10-induced neurodevelopmental toxicity in the zebrafish embryo/larvae.
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Encéfalo/efectos de los fármacos , Neuronas Dopaminérgicas/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Material Particulado/toxicidad , Animales , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Electroencefalografía , Embrión no Mamífero/efectos de los fármacos , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Locomoción/efectos de los fármacos , Contaminantes del Agua , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/embriologíaRESUMEN
Particulate matter (PM10) is one of the most important indicators of the pollution that characterizes air quality. Epidemiological studies have shown that PM10 can cause cardiovascular-related diseases in the population. And, we studied the developmental toxicity of PM10 and the underlying mechanism of its effects on the cardiovascular system of zebrafish embryo/larva. Changes in cardiac morphology, sinus venosus and bulbus arteriosus (SV-BA) distance, heart rate, vascular subintestinalis, blood flow, returned blood volume, and reactive oxygen species (ROS) level were measured, and changes in the expression levels of certain genes were assessed via RT-PCR. The results showed that PM10 caused a significant increase in pericardial sac area and SV-BA distance, a decrease in heart rate, inhibition of vascular subintestinalis growth, blood flow obstruction, reduced venous return, and other cardiovascular toxicities. PM10 induced an increase in the ROS level and significant increases in the expression levels of ERS signalling pathway factors and Nrf2 signalling pathway factors. The expression levels of the Wnt pathway-related genes also showed significant changes. Furthermore, ROS inhibitor N-Acetyl-l-cysteine (NAC) could ameliorate the cardiovascular toxicity of PM10 in zebrafish larvae. It is speculated that PM10 may result in cardiovascular toxicity by inducing higher ROS levels in the body, which could then induce ERS and lead to defects in the expression of genes related to the Wnt signalling pathway. The Nrf2 signalling pathway was activated as a stress compensatory mechanism during the early stage of PM10-induced cardiovascular injury. However, it was insufficient to counteract the PM10-induced cardiovascular toxicity.
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Sistema Cardiovascular/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Larva/efectos de los fármacos , Material Particulado/toxicidad , Animales , Larva/metabolismo , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Organogénesis , Especies Reactivas de Oxígeno/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genéticaRESUMEN
OBJECTIVE: Zebrafish inflammation models were used to evaluate the anti-inflammatory activity of isoniazid (INH) and preliminarily investigate the underlying mechanism. METHODS: Local, acute, and systemic zebrafish inflammation models were established by tail cutting, copper sulfate (CuSO4), and lipopolysaccharide (LPS) endotoxin treatments, respectively, to evaluate the anti-inflammatory activity of INH. Zebrafish in the inflammatory state were exposed to different concentrations of INH (1, 2, and 4 mM) for 72 h to observe changes in the migration and accumulation of inflammatory cells and measure the reactive oxygen species (ROS) content in zebrafish after INH treatment. The transcription levels of inflammation-related genes in zebrafish from all groups were measured using real-time polymerase chain reaction (RT-PCR). RESULTS: Compared to those observed in the control inflammation model group, the numbers of migrated and accumulated inflammatory cells in zebrafish in the INH-treated group significantly decreased. INH significantly decreased the ROS content induced by LPS. Compared to that observed in the LPS model group, INH at 1 and 2 mM significantly increased the expression of PPARγ and inhibited the expression of NF-κB, iκbαa, and AP-1 as well as the inflammatory factors TNF-É, TGF-ß, IL-1b, and COX-2. CONCLUSION: In this study, different zebrafish inflammation models were used to confirm that INH has anti-inflammatory activity. The associated mechanism may occur through the inhibition of ROS release, activation of PPARγ expression, inhibition of the transcriptional regulatory activity of NF-κB and AP-1, and reduction of INH inflammatory factor expression to relieve inflammation. The results of this study provide references for the clinical application of INH.
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Citocinas/metabolismo , Isoniazida/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Embrión no Mamífero/citología , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/metabolismo , Femenino , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolisacáridos/toxicidad , Masculino , FN-kappa B/metabolismo , PPAR gamma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción AP-1/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Pez Cebra/metabolismoRESUMEN
Two unique nitrogenous sesquiterpene quinone meroterpenoids, dysidinoid B (1) and dysicigyhone A (2), together with eight known analogues (3-10) were isolated and characterized from the marine sponge Dysidea septosa. Their structures with absolute configurations were established by a combination of extensive spectroscopic, electron circular dichroism (ECD) and single-crystal X-ray diffraction data analysis. Structurally, dysicigyhone A (2) possessed a unique benzo[d]oxazolidine-2-one unit. Additionally, dysidinoid B (1) exhibited significant anti-inflammatory effect by inhibiting TNF-α and IL-6 generation with IC50 values of 9.15 µM and 17.62 µM, respectively. Further in vivo anti-inflammatory assay verified that the dysidinoid B (1) alleviated the CuSO4-induced robust acute inflammatory response in zebrafish model.
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Antiinflamatorios/farmacología , Benzoquinonas/farmacología , Inflamación/tratamiento farmacológico , Nitrógeno/farmacología , Poríferos/química , Sesquiterpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Benzoquinonas/química , Células Cultivadas , Sulfato de Cobre , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Humanos , Inflamación/inducido químicamente , Interleucina-6/antagonistas & inhibidores , Interleucina-6/biosíntesis , Ratones , Modelos Moleculares , Estructura Molecular , Nitrógeno/química , Células RAW 264.7 , Sesquiterpenos/química , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/biosíntesis , Pez CebraRESUMEN
The charge-transfer process in transition-metal dichalcogenides (TMDCs) lateral homojunction affects the electron-hole recombination process of in optoelectronic devices. However, the optical properties of the homojunction reflecting the charge-transfer process has not been observed and studied. In this work, we investigated the charge-transfer-induced emission properties based on monolayer (1L)-bilayer (2L) WSe2 lateral homojunction with dozens of nanometer monolayer region. On the one hand, the photoluminescence (PL) emission of bilayer WSe2 from the homojunction area blue shifts â¼23 and â¼31 meV for direct and indirect bandgap emission, respectively, compared with the bare WSe2 bilayer region. The blue shift of the emission spectrum in the bilayer WSe2 is ascribed to the decrease in binding energy induced by charge transfer from monolayer to bilayer. On the other hand, the energy shift shows a tendency to increase as the temperature decreases. The energy blue shift is â¼57 meV for direct bandgap emission at 80 K, which is larger than that (â¼23 meV) at room temperature. The larger-energy blue shift at low temperature is derived from the larger driving force under larger band offset. Our observations of the unique optical properties induced by efficient charge transfer are very helpful for exploring novel TMDC-based optoelectronic devices.
RESUMEN
Isoniazid (INH) is a first-line anti-tuberculosis drug. INH has been detected in surface waters which may create a risk to aquatic organisms. In this study, the hepatotoxicity of INH was elucidated using zebrafish. The liver morphology, transaminase level, redox-related enzyme activity, reactive oxygen species (ROS) content and mRNA levels of liver injury-related genes were measured. The results showed that INH (4, 6â¯mM) significantly caused liver atrophy and increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in zebrafish. INH (6â¯mM) led to decreased catalase (CAT) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) content but increased ROS and malondialdehyde (MDA) levels. Moreover, INH (6â¯mM) decreased expression levels of miR-122 and pparα but increased mRNA levels of ap-1 and c-jun. Furthermore, mRNA levels of factors related to endoplasmic reticulum stress (ERS) (grp78, atf6, perk, ire1, xbp1s and chop), apoptosis (bax, cyt, caspase-3, caspase-8 and caspase-9) and the Nrf2 signalling pathway (nrf2, ho-1, nqo1, gclm and gclc) were significantly upregulated. INH may act on hepatotoxicity in zebrafish by increasing ROS content, which weakens the antioxidant capacity, leading to ERS, cell apoptosis and liver injury. In addition, the Nrf2 signalling pathway is activated as a stress compensation mechanism during INH-induced liver injury, but it is not sufficient to counteract INH-induced hepatotoxicity.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Isoniazida/toxicidad , Larva/metabolismo , Especies Reactivas de Oxígeno , Pez Cebra/metabolismo , Animales , Antioxidantes/metabolismo , Antituberculosos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Estrés del Retículo Endoplásmico/genética , Regulación de la Expresión Génica , Larva/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/efectos adversos , Transducción de Señal , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Isoniazid (INH) is a first-line antituberculosis drug. The incidence of adverse reactions accompanied by inflammation in the liver during drug administration to tuberculosis patients is high and severely affects clinical treatment. To better understand the mechanism of hepatotoxicity induced by INH under the inflammatory state, we compared the differences in levels of hepatotoxicity from INH between normal zebrafish and zebrafish in an inflammatory state to elucidate the hepatotoxic mechanism using different endpoints such as mortality, malformation, inflammatory effects, liver morphology, histological changes, transaminase analysis, and expression levels of certain genes. The results showed that the toxic effect of INH in zebrafish in an inflammatory state was more obvious than that in normal zebrafish, that liver size was significantly decreased as measured by liver fatty acid binding protein (LFABP) reporter fluorescence and intensity, and that alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly increased. Hematoxylin and eosin (HE) staining and electron microscopy showed that hepatocyte injury was more obvious in the inflammatory state. In the inflammatory state, INH significantly increased the expression levels of endoplasmic reticulum stress (ERS)-related factors (GRP78, ATF6, PERK, IRE1, XBP1s, GRP94, and CHOP), autophagy-related factors (beclin 1, LC3, Atg3, and Atg12), and apoptosis-related factors (caspase-3, caspase-8, caspase-9, Bax, p53, and Cyt) in larvae. Correlational analyses indicated that the transcription levels of the inflammatory factors interleukin-1b (IL-1b), tumor necrosis factor beta (TNF-ß), cyclooxygenase 2 (COX-2), and TNF-É were strongly positively correlated with ALT and AST. Furthermore, the ERS inhibitor sodium 4-phenylbutyrate (4-PBA) could ameliorate the hepatotoxicity of INH-lipopolysaccharide (LPS) in zebrafish larvae. These results indicated that INH hepatotoxicity was enhanced in the inflammatory state. ERS and its mediated autophagy and apoptosis pathways might be involved in INH-induced liver injury promoted by inflammation.
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Antituberculosos/efectos adversos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Isoniazida/efectos adversos , Lipopolisacáridos/toxicidad , Alanina Transaminasa/metabolismo , Animales , Apoptosis/efectos de los fármacos , Aspartato Aminotransferasas/metabolismo , Femenino , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Pez CebraRESUMEN
Metallic nanowires (NWs) support multiple surface plasmon (SP) modes, which lead to extraordinary SP propagation behaviors. The leaky SP modes in metallic NWs connect the guiding and radiation of light at the nanometer scale. Understanding and controlling these modes are of vital importance for various nanophotonic applications. Here, we investigate the radiation from two polarization-controlled SP modes on supported silver NWs by using leakage radiation imaging and Fourier imaging techniques. The radiation directions from these modes can be clearly resolved from the Fourier images. The radiation polarization of the SP modes is related to the polarization of the excitation light. By depositing thin Al2O3 films onto silver NWs or decreasing the excitation wavelength, the radiation angles and wave vectors of the two modes are increased, and the longitudinal mode is more sensitive to Al2O3 thickness. Moreover, the propagation length of the longitudinal mode is obtained by analyzing the leakage radiation images, which is decreased with the decrease of the excitation wavelength and the increase of the Al2O3 layer thickness. These results show that leakage radiation from different SP modes on silver NWs can be resolved directly and controlled effectively. The supported silver NWs can thus be applied to designing plasmonic circuits, nanoantennas and nanosensors.
RESUMEN
Plasmonics holds promise for the realization of miniaturized photonic devices and circuits in which light can be confined and controlled at the nanoscale using surface plasmon polaritons (SPPs), surface waves of collective oscillations of electrons at a metal/dielectric interface. However, realizing plasmonic applications fundamentally requires the ability to guide and transfer SPPs in different plasmonic structures. Here the generation and control of periodic collimated SPP-beams are reported in composite structures of silver nanowire on silver film with a dielectric spacer layer between them. It is revealed that the collimated beams on the silver film originate from the interference between film-SPPs generated by two SPP modes on the nanowire. The direction of the collimated beams can be readily tuned by changing the thickness of the dielectric spacer. These findings demonstrate the transfer of nanowire SPPs to film SPPs and offer a new approach to generate nondiffracting SPP-beams, which could facilitate the design and development of complex plasmonic systems for device applications and enable the tailoring of SPP radiation and SPP-matter interactions.