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BACKGROUND: Liver Hepatocellular carcinoma (LIHC) exhibits a high incidence of liver cancer with escalating mortality rates over time. Despite this, the underlying pathogenic mechanism of LIHC remains poorly understood. MATERIALS & METHODS: To address this gap, we conducted a comprehensive investigation into the role of G6PD in LIHC using a combination of bioinformatics analysis with database data and rigorous cell experiments. LIHC samples were obtained from TCGA, ICGC and GEO databases, and the differences in G6PD expression in different tissues were investigated by differential expression analysis, followed by the establishment of Nomogram to determine the percentage of G6PD in causing LIHC by examining the relationship between G6PD and clinical features, and the subsequent validation of the effect of G6PD on the activity, migration, and invasive ability of hepatocellular carcinoma cells by using the low expression of LI-7 and SNU-449. Additionally, we employed machine learning to validate and compare the predictive capacity of four algorithms for LIHC patient prognosis. RESULTS: Our findings revealed significantly elevated G6PD expression levels in liver cancer tissues as compared to normal tissues. Meanwhile, Nomogram and Adaboost, Catboost, and Gbdt Regression analyses showed that G6PD accounted for 46%, 31%, and 49% of the multiple factors leading to LIHC. Furthermore, we observed that G6PD knockdown in hepatocellular carcinoma cells led to reduced proliferation, migration, and invasion abilities. Remarkably, the Decision Tree C5.0 decision tree algorithm demonstrated superior discriminatory performance among the machine learning methods assessed. CONCLUSION: The potential diagnostic utility of G6PD and Decision Tree C5.0 for LIHC opens up a novel avenue for early detection and improved treatment strategies for hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Pronóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Algoritmos , Aprendizaje AutomáticoRESUMEN
BACKGROUND: As a rare heterogeneous kind of acute leukemia, mixed-phenotype acute leukemia (MPAL) co-expresses more than one cell lineage and could contain bilineal, biphenotypic, or a combination. MPAL is classified as T/myeloid, B/myeloid, B/T-lymphoid, and trilineage B/T/myeloid. METHOD: Here, we report a rare case of T/Myeloid bilineage mixed-phenotype acute leukemia with basophilia. RESULT: The puzzling morphological features are due to two distinct kinds of blasts have put hematologists into a dilemma. The diagnosis of T/myeloid MPAL with basophilia was established based on integrated diagnostics. CONCLUSIONS: To date, no case of a patient diagnosed with T/Myeloid bilineage MPAL with basophilia has been reported. The case focuses on the importance of an integrated diagnostic work-up, with a challenging morphological presentation and crucial role for flow cytometry.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Enfermedad Aguda , Leucocitos , Fenotipo , Citometría de Flujo , InmunofenotipificaciónRESUMEN
OBJECT: Pediatric diffuse intrinsic pontine glioma (DIPG) is a radiologically heterogeneous disease entity, here we aim to establish a multimodal imaging-based radiological classification and evaluate the outcome of different treatment strategies under this classification frame. METHODS: This retrospective study included 103 children diagnosed with DIPGs between January 2015 and August 2018 in Beijing Tiantan Hospital (Beijing, China). Multimodal radiological characteristics, including conventional magnetic resonance imaging (MRI), diffuse tensor imaging/diffuse tensor tractography (DTI/DTT), and positron emission tomography (PET) were reviewed to construct the classification. The outcome of different treatment strategies was compared in each DIPG subgroup using Kaplan-Meier method (log-rank test) to determine the optimal treatment for specific DIPGs. RESULTS: Four radiological DIPG types were identified: Type A ("homocentric", n=13), Type B ("ventral", n=41), Type C ("eccentric", n=37), and Type D ("dorsal", n=12). Their treatment modalities were grouped as observation (43.7%), cytoreductive surgery (CRS) plus radiotherapy (RT) (24.3%), RT alone (11.7%), and CRS alone (20.4%). CRS+RT mainly fell into type C (29.7%), followed by type B1 (21.9%) and type D (50%). Overall, CRS+RT exhibited a potential survival advantage compared to RT alone, which was more pronounced in specific type, but this did not reach statistical significance, due to limited sample size and unbalanced distribution. CONCLUSION: We proposed a multimodality imaging-based radiological classification for pediatric DIPG, which was useful for selecting optimal treatment strategies, especially for identifying candidates who may benefit from CRS plus RT. This classification opened a window into image-guided integrated treatment for pediatric DIPG.
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Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Niño , Humanos , Glioma/diagnóstico por imagen , Glioma/terapia , Estudios Retrospectivos , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Neoplasias del Tronco Encefálico/cirugía , Imagen MultimodalRESUMEN
BACKGROUND: Along with the wild applications of nitrogen-doped graphene quantum dots (N-GQDs) in the fields of biomedicine and neuroscience, their increasing exposure to the public and potential biosafety problem has gained more and more attention. Unfortunately, the understanding of adverse effects of N-GQDs in the central nervous system (CNS), considered as an important target of nanomaterials, is still limited. RESULTS: After we found that N-GQDs caused cell death, neuroinflammation and microglial activation in the hippocampus of mice through the ferroptosis pathway, microglia was used to assess the molecular mechanisms of N-GQDs inducing ferroptosis because it could be the primary target damaged by N-GQDs in the CNS. The microarray data suggested the participation of calcium signaling pathway in the ferroptosis induced by N-GQDs. In microglial BV2 cells, when the calcium content above the homeostatic level caused by N-GQDs was reversed, the number of cell death, ferroptosis alternations and excessive inflammatory cytokines release were all alleviated. Two calcium channels of L-type voltage-gated calcium channels (L-VGCCs) in plasma membrane and ryanodine receptor (RyR) in endoplasmic reticulum (ER) took part in N-GQDs inducing cytosolic calcium overload. L-VGCCs and RyR calcium channels were also involved in promoting the excess iron influx and triggering ER stress response, respectively, which both exert excessive ROS generation and result in the ferroptosis and inflammation in BV2 cells. CONCLUSION: N-GQDs exposure caused ferroptosis and inflammatory responses in hippocampus of mice and cultured microglia through activating two calcium channels to disrupt intracellular calcium homeostasis. The findings not only posted an alert for biomedical applications of N-GQDs, but also highlighted an insight into mechanism researches of GQDs inducing multiple types of cell death in brain tumor therapy in the future.
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Ferroptosis , Grafito , Puntos Cuánticos , Calcio , Canales de Calcio , Grafito/toxicidad , Homeostasis , Microglía , Nitrógeno , Puntos Cuánticos/toxicidadRESUMEN
Hemorrhage of brainstem cavernous malformation (CM) would cause various symptoms and severe disability. The study aimed to elaborate on the 5-year actuarial cumulative hazard of symptomatic hemorrhage. Patients diagnosed in our institute between 2009 and 2013 were prospectively registered. All clinical data were obtained, follow-up was performed, and risk factors were evaluated. Four hundred sixty-eight patients (217 female, 46.4%) were included in the study with a median follow-up duration of 79.0 months. A total of 137 prospective hemorrhages occurred in 107 patients (22.9%) during 1854.0 patient-years. Multivariate Cox analysis found age ≥ 55 years (hazard ratio (HR) 2.166, p = 0.002), DVA (HR 1.576, p = 0.026), superficial-seated location (HR 1.530, p = 0.047), and hemorrhage on admission (HR 2.419, p = 0.026) as independent risk factors for hemorrhage. The 5-year cumulative hazard of hemorrhage was 30.8% for the overall cohort, 47.8% for 60 patients with age ≥ 55 years, 43.7% for 146 patients with DVA, 37.9% for 272 patients with superficial-seated lesions, and 37.2% for 341 patients with hemorrhage on admission. As a stratified analysis, within subcohort of 341 patients with a hemorrhagic presentation, age ≥ 55 years (HR 3.005, p < 0.001), DVA (HR 1.801, p = 0.010), and superficial-seated location (HR 2.276, p = 0.001) remained independently significant. The 5-year cumulative hazard of hemorrhage was 52.0% for 119 patients with both DVA and hemorrhagic presentation. The 5-year cumulative hemorrhagic risk was 30.8% and was higher in subgroups if harboring risk factors that helped to predict potential hemorrhagic candidates and were useful for treatment decision-making.Clinical Trial Registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR-POC-17011575.
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Hemangioma Cavernoso del Sistema Nervioso Central , Hemorragia , Tronco Encefálico/anomalías , Tronco Encefálico/patología , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/etiología , Estudios de Cohortes , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Hemorragia/epidemiología , Hemorragia/etiología , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
Titanium dioxide (TiO2 ) is generally regarded as a nontoxic and nongenotoxic white mineral, which is mainly applied in the manufacture of paper, paint, plastic, sunscreen lotion and other products. Recently, TiO2 nanoparticles (TiO2 NPs) have been demonstrated to cause chronic inflammation and lung tumor formation in rats, which may be associated with the particle size of TiO2 . Considering the important role of activator protein-1 (AP-1) in regulating multiple genes involved in the cell proliferation and inflammation and the induction of neoplastic transformation, we aimed to evaluate the potency of TiO2 NPs (≤ 20 nm) on the activation of AP-1 signaling pathway and the generation of reactive oxygen species (ROS) in a mouse epidermal cell line, JB6 cells. MTT, electron spin resonance (ESR), AP-1 luciferase activity assay in vitro and in vivo, and Western blotting assay were used to clarify this problem. Our results indicated that TiO2 NPs dose-dependently caused the hydroxyl radical (·OH) generation and sequentially increased the AP-1 activity in JB6 cells. Using AP-1-luciferase reporter transgenic mice models, an obvious increased AP-1 activity was detected in dermal tissue after exposure to TiO2 NPs for 24 h. Interestingly, TiO2 NPs increased the AP-1 activity via stimulating the expression of mitogen-activated protein kinases (MAPKs) family members, including extracellular signal-regulated protein kinases (ERKs), p38 kinase, and C-Jun N-terminal kinases (JNKs). Of note, the AP-1 activation induced by TiO2 NPs could be blocked by specific inhibitors (SB203580, PD98059, and SP 600125, respectively) that inhibit ERKs and p38 kinase but not JNKs. These findings indicate that ROS generation is involved in TiO2 NPs-induced AP-1 activation mediated by MAPKs signal pathway.
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Nanopartículas , Factor de Transcripción AP-1 , Animales , Quinasas MAP Reguladas por Señal Extracelular , Proteínas Quinasas JNK Activadas por Mitógenos , Sistema de Señalización de MAP Quinasas , Ratones , Nanopartículas/toxicidad , Ratas , Especies Reactivas de Oxígeno , Titanio , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Cisplatin resistance of non-small-cell lung cancer (NSCLC) needs to be well elucidated. RING finger protein (RNF38) has been proposed as a biomarker of NSCLC poor prognosis. However, its role in drug resistance in NSCLC is poorly understood. RNF38 expression was detected in normal lung epithelial cell and four NSCLC cell lines. RNF38 was stably overexpressed in A549 and H460 cells or silenced in H1975 and cisplatin-resistant A549 cells (A549-CDDP resistant) using lentiviral vectors. RNF38 expression levels were determined using quantitative real-time polymerase chain reaction and western blotting analysis. Cell viability in response to different concentrations of cisplatin was evaluated by Cell Counting Kit-8 assay. RNF38 expression levels were markedly elevated in NSCLC cells and cells harboring high RNF38 were less sensitive to cisplatin. Overexpression of RNF38 reduced, while RNF38 silencing increased the drug sensitivity of cisplatin in NSCLC cells. Cisplatin-resistant cells expressed high RNF38 level. RNF38 silencing promoted cell apoptosis and enhanced the drug sensitivity of cisplatin in cisplatin-resistant NSCLC cells. These findings indicate that RNF38 might induce cisplatin resistance of NSCLC cells via promoting cell apoptosis and RNF38 could be a novel target for rectify cisplatin resistance in NSCLC cases.
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Carcinoma de Pulmón de Células no Pequeñas , Proteínas Portadoras/fisiología , Resistencia a Antineoplásicos , Neoplasias Pulmonares , Células A549 , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Supervivencia Celular , Cisplatino/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismoRESUMEN
With the rapid development of nanotechnology, new nanomaterials with enormous potentials continue to emerge, especially metal nanomaterials. Metal nanomaterials possess the characteristics of metals and nanomaterials, so they are widely used in many fields. But at the same time, whether the use or release of metal nan4omaterials into the environment is toxic to human beings and animals has now attained widespread attention at home and abroad. Currently, it is an indisputable fact that cancer ranks among the top causes of death among residents worldwide. The properties of causing DNA damage and mutations possessed by these metal nanomaterials make them unpredictable influences in the body, subsequently leading to genotoxicity and carcinogenicity. Due to the increasing evidence of their roles in carcinogenicity, this article reviews the toxicological and carcinogenic effects of metal nanomaterials, including nano-metal elements (nickel nanoparticles, silver nanoparticles, and cobalt nanoparticles) and nano-metal oxides (titanium dioxide nanoparticles, silica nanoparticles, zinc oxide nanoparticles, and alumina nanoparticles). This article provides a reference for the researchers and policymakers to use metal nanomaterials rationally in modern industries and biomedicine.
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Pruebas de Carcinogenicidad , Carcinógenos/toxicidad , Nanopartículas del Metal/toxicidad , Nanoestructuras/toxicidad , Animales , HumanosRESUMEN
Silver nanoparticles (AgNPs) have become widespread in the environment with increasing industrial applications. But the studies about their potential health risks are far from enough, especially in neurotoxic effects. This study aimed to investigate the neurotoxic effects of longer-term exposure (prolonged exposure for 48 h and chronic exposure for 6 days) of 20nm AgNPs with/without polyvinylpyrrolidone (PVP) coating at low concentrations (0.01-10 mg·L-1 ) to Caenorhabditis elegans. The results suggested that exposure to AgNPs induced damage to nematode survival, with the longest and relative average life span reduced. Exposure to AgNPs caused neurotoxicity on locomotion behaviors (head thrashes, body bends, pharyngeal pumping frequency, and defecation interval) and sensory perception behaviors (chemotaxis assay and thermotaxis assay), as well as impaired dopaminergic, GABAergic, and cholinergic neurons, except for glutamatergic, based on the alters fluorescence intensity, in a dose- and time-dependent manner. Further investigations suggested that the low-dose AgNPs (0.01-0.1 mg·L-1 ) exposure raises receptors of GABAergic and dopamine in C. elegans at the genetic level, whereas opposite results were observed at higher doses (1-10 mg·L-1 ), which implied that AgNPs could cause neurotoxicity by impairing neurotransmitter delivery. The PVP-AgNPs could cause a higher fatality rate and neurotoxicity at the same dose. Notably, AgNPs did not cause any deleterious effect on nematodes at the lowest dose of 0.01 mg·L-1 . In general, these results suggested that AgNPs possess the neurotoxic potential in C. elegans and provided useful information to understand the neurotoxicity of AgNPs, which would offer an inspiring perspective on the safe application.
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Caenorhabditis elegans/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Neuronas/efectos de los fármacos , Povidona/toxicidad , Plata/toxicidad , Animales , Caenorhabditis elegans/fisiología , Neuronas/fisiología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Excipientes Farmacéuticos/toxicidad , Sustitutos del Plasma/toxicidadRESUMEN
OBJECTIVE: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) have the ability to noninvasively visualize changes in white matter tracts, as well as their relationships with lesions and other structures. DTI/DTT has been increasingly used to improve the safety and results of surgical treatment for lesions in eloquent areas, such as brainstem cavernous malformations. This study aimed to investigate the application value of DTI/DTT in brainstem glioma surgery and to validate the spatial accuracy of reconstructed corticospinal tracts (CSTs). METHODS: A retrospective analysis was performed on 54 patients with brainstem gliomas who had undergone surgery from January 2016 to December 2018 at Beijing Tiantan Hospital. All patients underwent preoperative DTI and tumor resection with the assistance of DTT-merged neuronavigation and electrophysiological monitoring. Preoperative conventional MRI and DTI data were collected, and the muscle strength and modified Rankin Scale (mRS) score before and after surgery were measured. The surgical plan was created with the assistance of DTI/DTT findings. The accuracy of DTI/DTT was validated by performing direct subcortical stimulation (DsCS) intraoperatively. Multiple linear regression was used to investigate the relationship between quantitative parameters of DTI/DTT (such as the CST score and tumor-to-CST distance [TCD]) and postoperative muscle strength and mRS scores. RESULTS: Among the 54 patients, 6 had normal bilateral CSTs, 12 patients had unilateral CST impairments, and 36 had bilateral CSTs involved. The most common changes in the CSTs were deformation (n = 29), followed by deviation (n = 28) and interruption (n = 27). The surgical approach was changed in 18 cases (33.3%) after accounting for the DTI/DTT results. Among 55 CSTs on which DsCS was performed, 46 (83.6%) were validated as spatially accurate by DsCS. The CST score and TCD were significantly correlated with postoperative muscle strength (r = -0.395, p < 0.001, and r = 0.275, p = 0.004, respectively) and postoperative mRS score (r = 0.430, p = 0.001, and r = -0.329, p = 0.015, respectively). The CST score was independently linearly associated with postoperative muscle strength (t = -2.461, p = 0.016) and the postoperative mRS score (t = 2.052, p = 0.046). CONCLUSIONS: DTI/DTT is a valuable tool in the surgical management of brainstem gliomas. With good accuracy, it can help optimize surgical planning, guide tumor resection, and predict the postoperative muscle strength and postoperative quality of life of patients.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/cirugía , Imagen de Difusión Tensora , Glioma/diagnóstico por imagen , Glioma/cirugía , Humanos , Tractos Piramidales/diagnóstico por imagen , Tractos Piramidales/cirugía , Calidad de Vida , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Tumor necrosis factor-α (TNF-α) is a pluripotent mediator of pro-inflammatory and antimicrobial defense mechanisms and a regulator of lymphoid organ development. Although two types of TNF-α have been identified in several teleost species, their functions in pathogen infection remain largely unexplored, especially in pathogen clearance. Herein, we cloned and characterized two types of TNF-α, termed shTNF-α1 and shTNF-α2, and their receptors, shTNFR1 and shTNFR2, from snakehead (Channa argus). These genes were constitutively expressed in all tested tissues, and were induced by Aeromonas schubertii and Nocardia seriolae in head kidney and spleen in vivo, and by lipoteichoic acid (LTA), lipopolysaccharides (LPS), and Polyinosinic-polycytidylic acid [Poly (I:C)] in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shTNF-α1 and shTNF-α2 upregulated the expression of endogenous shTNF-α1, shTNF-α2, shTNFR1, and shTNFR2, and enhanced intracellular bactericidal activity, with shTNF-α1 having a greater effect than shTNF-α2. These findings suggest important roles of fish TNFα1, TNFα2, and their receptors in bacterial infection and pathogen clearance, and provide a new insight into their function in antibacterial innate immunity.
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Enfermedades de los Peces/inmunología , Peces/genética , Peces/inmunología , Inmunidad Innata/genética , Receptores del Factor de Necrosis Tumoral/genética , Factor de Necrosis Tumoral alfa/genética , Aeromonas/fisiología , Animales , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Riñón Cefálico/inmunología , Leucocitos/inmunología , Lipopolisacáridos/farmacología , Nocardia/fisiología , Nocardiosis/inmunología , Nocardiosis/veterinaria , Poli I-C/farmacología , Receptores del Factor de Necrosis Tumoral/inmunología , Bazo/inmunología , Ácidos Teicoicos/farmacología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
As a central pro-inflammatory cytokine, interleukin-1ß (IL-1ß) plays critical roles in the inflammatory response, pathogen infection, and immunological challenges in mammals. Although fish IL-1ß has been confirmed to participate in inflammatory response to pathogen infection, few studies have been performed to characterize the antibacterial and bactericidal functions of fish IL-1ß. In this study, snakehead (Channa argus) IL-1ß (shIL-1ß) and its receptors, shIL-1R1 and shIL-1R2, were cloned and functionally characterized. ShIL-1ß contained the IL-1 family signature domain, and a potential cutting site at Asp96 that presented in all vertebrate IL-1ß sequences. ShIL-1R1 had three extracellular IG-like domains and one intracellular signal TIR domain, while shIL-1R2 had three extracellular IG-like domain but lacked the intracellular signal TIR domain. ShIL-1ß, shIL-1R1, and shIL-1R2 were constitutively expressed in all tested tissues, and their expressions could be induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo, and by LTA, LPS, and Poly (I:C) in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shIL-1ß upregulated the expression of endogenous shIL-1ß, shIL-R1, and shIL-R2 in snakehead HKLs, and enhanced intracellular bactericidal activity. Taken together, this study found that, like IL-1ß and its receptors in mammals, shIL-1ß and its receptors play crucial roles in antibacterial innate immunity. This provides new insight into the evolution of IL-1ß function in vertebrates.
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Bacterias/inmunología , Infecciones Bacterianas/veterinaria , Carpas/inmunología , Enfermedades de los Peces/inmunología , Inmunidad Innata , Interleucina-1beta/genética , Receptores de Interleucina-1/genética , Animales , Antibacterianos , Infecciones Bacterianas/inmunología , Carpas/genética , Carpas/microbiología , Clonación Molecular , Enfermedades de los Peces/microbiología , Riñón Cefálico/inmunología , Interleucina-1beta/inmunología , Receptores de Interleucina-1/inmunologíaRESUMEN
BACKGROUND: Graphene quantum dots (GQDs) provide a bright prospect in the biomedical application because they contain low-toxic compounds and promise imaging of deep tissues and tiny vascular structures. However, the biosafety of this novel QDs has not been thoroughly evaluated, especially in the central nervous system (CNS). The microarray analysis provides a hint that nitrogen-doped GQDs (N-GQDs) exposure could cause ferroptosis in microglia, which is a novel form of cell death dependent on iron overload and lipid peroxidation. RESULTS: The cytosolic iron overload, glutathione (GSH) depletion, excessive reactive oxygen species (ROS) production and lipid peroxidation (LPO) were observed in microglial BV2 cells treated with N-GQDs, which indicated that N-GQDs could damage the iron metabolism and redox balance in microglia. The pre-treatments of a specific ferroptosis inhibitor Ferrostatin-1 (Fer-1) and an iron chelater Deferoxamine mesylate (DFO) not only inhibited cell death, but also alleviated iron overload, LPO and alternations in ferroptosis biomarkers in microglia, which were caused by N-GQDs. When assessing the potential mechanisms of N-GQDs causing ferroptosis in microglia, we found that the iron content, ROS generation and LPO level in mitochondria of BV2 cells all enhanced after N-GQDs exposure. When the antioxidant ability of mitochondria was increased by the pre-treatment of a mitochondria targeted ROS scavenger MitoTEMPO, the ferroptotic biological changes were effectively reversed in BV2 cells treated with N-GQDs, which indicated that the N-GQDs-induced ferroptosis in microglia could be attributed to the mitochondrial oxidative stress. Additionally, amino functionalized GQDs (A-GQDs) elicited milder redox imbalance in mitochondria and resulted in less ferroptotic effects than N-GQDs in microglia, which suggested a slight protection of amino group functionalization in GQDs causing ferroptosis. CONCLUSION: N-GQDs exposure caused ferroptosis in microglia via inducing mitochondrial oxidative stress, and the ferroptotic effects induced by A-GQDs were milder than N-GQDs when the exposure method is same. This study will not only provide new insights in the GQDs-induced cell damage performed in multiple types of cell death, but also in the influence of chemical modification on the toxicity of GQDs.
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Ferroptosis/fisiología , Mitocondrias/fisiología , Estrés Oxidativo/fisiología , Puntos Cuánticos/toxicidad , Antioxidantes , Apoptosis , Muerte Celular , Ciclohexilaminas , Glutatión , Grafito , Humanos , Hierro , Peroxidación de Lípido , Microglía , Mitocondrias/efectos de los fármacos , Oxidación-Reducción , Fenilendiaminas , Especies Reactivas de OxígenoRESUMEN
With the development of high-power lasers for aerospace, electronics, etc., the demand for large-aperture planar optical elements has become more urgent, along with the demand for measurement methods. In this paper, the design of a 300 mm aperture vertical Fizeau spatial-temporal phase-shifting interferometer is discussed. Based on position difference between laser sources, the spatial phase-shifting technique is achieved by generating a laser source array on the focal plane of the collimation lens, and four pairs of coherent beams with different phase shifts are integrated in a vertical Fizeau interference system. Combined with a tunable laser diode, a temporal phase-shifting technique can be realized in any pair of coherent beams through wavelength tuning. The key techniques, which include laser duplication to introduce different phase shifts, conjugate imaging, and separation for interferograms, and assembly for a transmission flat, are demonstrated. The systematic error and position mismatch error of interferograms are eliminated. Comparison experiments are conducted between spatial and temporal phase-shifting techniques. A dynamic water surface is also measured to verify its capacity for detecting dynamic objects.
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This study evaluated the biodistribution and organ oxidative effects of silver nanoparticles (AgNPs) coated with/without polyvinylpyrrolidone (PVP) (AgNP-20 and AgNP-PVP) in mice; these were administered by gavage at a dose of 10-250 mg/kg body weight per day for 28 days. The results showed that both the AgNPs could induce subacute toxicity and oxidative damage to mice and were mainly accumulated in the liver and spleen and excreted by feces. AgNPs could be absorbed into blood and might cross the blood-brain barrier, and be distributed extensively in mice. The malondialdehyde content in the liver, lungs and kidneys increased in both AgNP groups, while the content of glutathione decreased, and the activity of superoxide dismutase increased at first and then decreased along with the increased doses. Inflammatory pathological changes in the lung and liver at high dose of both AgNPs were consistent with increases in glutamate pyruvic transaminase, glutamate oxaloacetic transaminase and the total protein in serum detection. The Ag content was detected in organs, with the highest content in the liver, followed by spleen, while the Ag content in feces was about 500 times higher than that in urine. AgNP-PVP could induce higher oxidative stress and subacute toxicity than AgNP-20 at the same dose, which might be related to the higher concentrations and more Ag+ ions released in mice after AgNP-PVP exposure. The data from this research provided information on toxicity and biodistribution of AgNPs following gavage administration in mice, and might shed light for future application of AgNPs in daily life.
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Nanopartículas del Metal/toxicidad , Povidona/toxicidad , Compuestos de Plata/toxicidad , Administración Oral , Animales , Femenino , Masculino , Nanopartículas del Metal/administración & dosificación , Ratones Endogámicos ICR , Povidona/metabolismo , Compuestos de Plata/administración & dosificación , Compuestos de Plata/metabolismo , Distribución TisularRESUMEN
As a kind of conventional metal nanomaterial, nickel nanoparticles (Ni NPs) have broad application prospects in the fields of magnetism, energy technology and biomedicine and have quickly attracted great interest. The potential negative effects of Ni NPs have also attracted wide attention from some researchers. Studies have shown that Ni NPs cause a variety of toxic effects on cells, animals and humans and have toxic effects of multiple systems such as respiratory system, cardiovascular system and reproductive system. Ni NPs can lead to oxidative stress, apoptosis, DNA damage and inflammation and induce the increase of intracellular reactive oxygen species. The toxicity of Ni NPs is also found to be related to the mitogen-activated protein kinase pathway and the hypoxia inducible factor-1α pathway. Therefore, the toxicity and mechanism of Ni NPs are reviewed in this paper, and the future researches in this field are also proposed.
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Nanopartículas del Metal/toxicidad , Níquel/toxicidad , Animales , Apoptosis/efectos de los fármacos , Daño del ADN , Humanos , Nanopartículas del Metal/química , Níquel/química , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
As a new type of nanomaterials, nickel nanoparticles (Ni NPs) have been widely used by human beings, whose exposure probability was greatly increasing. Many studies have shown that Ni NPs can induce apoptosis, oxidative stress and DNA damage. Nowadays, male reproductive health is an important public health problem, which is a hot topic in toxicological research. In the present study, to protect reproductive health, the effect of Ni NPs exposure on spermatogenesis injury was assessed, understanding the toxicity and safety of Ni NPs. Sixty ICR male mice with 20 ± 2 g were randomly divided into five groups. The experimental groups were treated with 5 mg/kg, 15 mg/kg and 45 mg/kg Ni NPs. The reproductive toxicity of Ni NPs on male mice was evaluated by the indexes of testicular organ coefficient, testicular marker enzyme, sperm motility and histopathology. As a result, the somatic index of testis and epididymis increased in each group. Compared with the control group, the activity of testicular markers increased and the sperm motility index decreased in the low-, middle- and high-dose groups. Pathological results indicated that various cell apoptosis and disordered arrangement of cells occurred in the seminiferous tubules of the exposed groups. In conclusion, the findings of this study suggest that Ni NPs have certain damage to spermatogenesis in mice.
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Níquel/toxicidad , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Epidídimo/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Nanopartículas , Estrés Oxidativo/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatozoides/patología , Testículo/patologíaRESUMEN
The major cause of mortality for prostate cancer (PCa) is metastasis; however, the metastatic mechanism remains unclear. MicroRNAs (miRNAs) alter the expression patterns of essential genes through posttranscriptional regulation during cancer development. The study was mainly aimed at identifying specific miRNA-messenger RNA (mRNA) interactions and signaling pathways associated with PCa distant metastasis. New analytical approaches were applied, combining miRNA and gene expression microarray, to screen differentially expressed miRNA-mRNA pairs in the normal prostate epithelial cell line RWPE-1, the highly-metastatic human PCa cell line PC-3M-1E8 (H-1E8 or 1E8) and the lowly metastatic cell line PC-3M-2B4 (L-2B4 or 2B4). Eight differentially expressed candidate miRNAs and their targets closely related to PCa metastasis were identified and validated in patients by using the Gene Expression Omnibus database. Among them, overexpression of hsa-miR-92b-3p and hsa-let-7a-5p and underexpression of their targets, such as glutathione-S-transferase M3 (GSTM3), baculoviral IAP repeat-containing 3, and cyclin-dependent kinase inhibitor 1 (CDKN1A), were also validated in H-1E8 cells compared with L-2B4 cells. Bioinformatics suggested that hsa-miR-92b-3p and hsa-let-7a-5p and their targets might promote PCa metastasis through platinum-based drug resistance and the JAK-STAT signaling pathway. H-1E8 and L-2B4 cells treated by cisplatin showed the greatly decreased levels of hsa-miR-92b-3p and hsa-let-7a-5p; however, in contrast to 2B4 cells, 1E8 cells did not negatively regulate the increase in the expression levels of the targets GSTM3 and CDKN1A. This finding suggests that the dysregulation between hsa-let-7a-5p/CDKN1A and hsa-miR-92b-3p/GSTM3 pairs is associated with platinum-based chemoresistance of metastatic cancer cells.
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Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , ARN Mensajero/genética , Transducción de Señal/genética , Animales , Línea Celular Tumoral , Cisplatino/farmacología , Bases de Datos Genéticas , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Humanos , Masculino , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Modelos Biológicos , Metástasis de la Neoplasia , ARN Mensajero/metabolismo , Reproducibilidad de los ResultadosRESUMEN
With the rapid expansion of human exposure to silver nanoparticles (AgNPs), the genotoxicity screening is critical to the biosafety evaluation of nanosilver. This study assessed DNA damage and chromosomal aberration in the human hepatoma cell line (HepG2) as well as the effects on the micronucleus of bone marrow in mice induced by 20 nm polyvinylpyrrolidone-coated nanosilver (PVP-AgNPs) and 20 nm bare nanosilver (AgNPs). Our results showed that the two types of AgNPs, in doses of 20-160 µg/mL, could cause genetic toxicological changes on HepG2 cells. The DNA damage degree of HepG2 cells in 20 nm AgNPs was higher than that in 20 nm PVP-AgNPs, while the 20 nm PVP-AgNPs caused more serious chromosomal aberration than 20 nm AgNPs. Both kinds of AgNPs caused genetic toxicity in a dose-dependent manner in HepG2 cells. In the micronucleus test on mouse bone marrow cells, in doses of 10, 50 and 250 mg/kg body weight administered orally for 28 days once a day, the two kinds of AgNPs have no obvious inhibitory effect on the mouse bone marrow cells, and the effect of chromosome aberration could be documented at the high dose of 250 mg/kg. These results suggest that AgNPs have genotoxic effects in HepG2 cells and limited effects on bone marrow in mice; both in vitro and in vivo tests could be of great importance on the evaluation of genotoxicity of nanosilver. These findings can provide useful toxicological information that can help to assess genetic toxicity of nanosilver in vitro and in vivo.
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Aberraciones Cromosómicas/inducido químicamente , Daño del ADN , Hígado/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Animales , Apoptosis/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Femenino , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Pruebas de MicronúcleosRESUMEN
Microglial cells are resident immune cells in the central nervous system. Activation of microglia as induced by CdTe quantum dots (QDs) can trigger damage to neurons. To quantify the intracellular QDs, we monitored the intracellular Cd concentration in the QD-exposed mouse microglial cells (BV-2 cell line). The extent of cell injury at different times correlated with the Cd concentration in cells at that time. In addition to Cd ion detection, we also monitored the intracellular fluorescence of the QDs. More QDs accumulated in the nucleus than in the cytoplasm. Comet assays confirmed that QDs induce DNA damage. However, DNA cannot interact with QDs, so the DNA damage was not caused by CdTe QDs adducts to DNA but by the increase of the Cd ion concentration and the secondary oxidative damage. In addition to DNA damage, biofilm injury and endogenous reduced glutathione depletion were also apparent in QD-exposed BV-2 cells. These changes can be prevented or even reversed by exogenous reduced glutathione administration.