RESUMEN
Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.
Asunto(s)
Desinfectantes , Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/metabolismo , Guanidina/toxicidad , Guanidina/metabolismo , Ratones Endogámicos C57BL , Aerosoles y Gotitas Respiratorias , Pulmón , Guanidinas/metabolismo , Macrófagos , Desinfectantes/farmacología , LípidosRESUMEN
Inhaling polyhexamethylene guanidine (PHMG) aerosol, a broad-spectrum disinfectant, can lead to severe pulmonary fibrosis. Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, is believed to play a role in the chemical-induced pulmonary injury. This study aimed to investigate the mechanism of ferroptosis in the progression of PHMG-induced pulmonary fibrosis. C57BL/6â¯J mice and the alveolar type II cell line MLE-12 were used to evaluate the toxicity of PHMG in vivo and in vitro, respectively. The findings indicated that iron deposition was observed in PHMG induced pulmonary fibrosis mouse model and ferroptosis related genes have changed after 8 weeks PHMG exposure. Additionally, there were disturbances in the antioxidant system and mitochondrial damage in MLE-12 cells following a 12-hour treatment with PHMG. Furthermore, the study observed an increase in lipid peroxidation and a decrease in GPX4 activity in MLE-12 cells after exposure to PHMG. Moreover, pretreatment with the ferroptosis inhibitors Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) not only restored the antioxidant system and GPX4 activity but also mitigated lipid peroxidation. Current data exhibit the role of ferroptosis pathway in PHMG-induced pulmonary fibrosis and provide a potential target for future treatment.
Asunto(s)
Ferroptosis , Guanidinas , Peroxidación de Lípido , Ratones Endogámicos C57BL , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Fibrosis Pulmonar , Animales , Ferroptosis/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Ratones , Peroxidación de Lípido/efectos de los fármacos , Línea Celular , Guanidinas/toxicidad , Guanidinas/farmacología , Masculino , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/patología , Ciclohexilaminas/farmacología , Fenilendiaminas , Quinoxalinas , Compuestos de EspiroRESUMEN
The pre-research of medical device standards is of great significance for the enactment and amendment of standards. This study discusses four aspects and explores how to promote more scientific and reasonable pre-research. Based on the pre-research practice of medical device standards project, this study puts forward relevant work ideas and suggestions.
Asunto(s)
Equipos y Suministros , Equipos y Suministros/normasRESUMEN
BACKGROUND: Carbon dots (CDs), as excellent antibacterial nanomaterials, have gained great attention in treating infection-induced diseases such as periodontitis and stomatitis. Given the eventual exposure of CDs to the intestine, elucidating the effect of CDs on intestinal health is required for the safety evaluation of CDs. RESULTS: Herein, CDs extracted from ε-poly-L-lysine (PL) were chosen to explore the modulation effect of CDs on probiotic behavior in vitro and intestinal remodeling in vivo. Results verify that PL-CDs negatively regulate Lactobacillus rhamnosus (L. rhamnosus) growth via increasing reactive oxygen species (ROS) production and reducing the antioxidant activity, which subsequently destroys membrane permeability and integrity. PL-CDs are also inclined to inhibit cell viability and accelerate cell apoptosis. In vivo, the gavage of PL-CDs is verified to induce inflammatory infiltration and barrier damage in mice. Moreover, PL-CDs are found to increase the Firmicutes to Bacteroidota (F/B) ratio and the relative abundance of Lachnospiraceae while decreasing that of Muribaculaceae. CONCLUSION: Overall, these evidences indicate that PL-CDs may inevitably result in intestinal flora dysbiosis via inhibiting probiotic growth and simultaneously activating intestinal inflammation, thus causing pathological damage to the intestine, which provides an effective and insightful reference for the potential risk of CDs from the perspective of intestinal remodeling.
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Carbono , Microbioma Gastrointestinal , Animales , Ratones , Carbono/farmacología , Disbiosis , Intestinos , InflamaciónRESUMEN
BACKGROUND: Chronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown. RESULTS: We applied an ex vivo endothelial biosensor assay for serum samples from 133 diesel engine testers (DETs) and 126 non-DETs with the aim of identifying evidence of increased risk for cardiovascular diseases. Environmental monitoring suggested that DETs were exposed to high levels of diesel exhaust aerosol (282.3 µg/m3 PM2.5 and 135.2 µg/m3 elemental carbon). Surprisingly, chronic diesel exhaust exposure was associated with a pro-inflammatory phenotype in the ex vivo endothelial cell model, in a dose-dependent manner with CCL5 and VCAM as most affected genes. This dysfunction was not mediated by reduction in circulatory pro-inflammatory factors but significantly associated with a reduction in circulatory metabolites cGMP and an increase in primary DNA damage in leucocyte in a dose-dependent manner, which also explained a large magnitude of association between diesel exhaust exposure and ex vivo endothelial biosensor response. Exogenous cGMP addition experiment further confirmed the induction of ex vivo biosensor gene expressions in endothelial cells treated with physiologically relevant levels of metabolites cGMP. CONCLUSION: Serum-borne bioactivity caused the arterial endothelial cell dysfunction may attribute to the circulatory metabolites based on the ex vivo biosensor assay. The reduced cGMP and increased polycyclic aromatic hydrocarbons metabolites-induced cyto/geno-toxic play important role in the endothelial cell dysfunction of workers chronic exposure to diesel exhaust.
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Enfermedades Cardiovasculares , Emisiones de Vehículos , Células Endoteliales , Humanos , Emisiones de Vehículos/toxicidadRESUMEN
OBJECTIVE: Iron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers. METHODS: We studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses. RESULTS: The average annual change of lung function was - 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and - 34.36 ml/year in forced vital capacity (FVC) in males, and - 39.06 ml/year in FEV1 and - 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC. CONCLUSIONS: Our findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.
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Polvo , Mediadores de Inflamación/sangre , Hierro , Obreros Metalúrgicos , Exposición Profesional/efectos adversos , Espirometría/métodos , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Exposición por Inhalación/efectos adversos , Recuento de Leucocitos/métodos , Estudios Longitudinales , Masculino , Exposición Profesional/análisisRESUMEN
BACKGROUND: Diesel exhaust (DE) is a major source of ultrafine particulate matters (PM) in ambient air and contaminates many occupational settings. Airway remodeling assessed using computerized tomography (CT) correlates well with spirometry in patients with obstructive lung diseases. Structural changes of small airways caused by chronic DE exposure is unknown. Wall and lumen areas of 6th and 9th generations of four candidate airways were quantified using end-inhalation CT scans in 78 diesel engine testers (DET) and 76 non-DETs. Carbon content in airway macrophage (CCAM) in sputum was quantified to assess the dose-response relationship. RESULTS: Environmental monitoring and CCAM showed a much higher PM exposure in DETs, which was associated with higher wall area and wall area percent for 6th generation of airways. However, no reduction in lumen area was identified. No study subjects met spirometry diagnosis of airway obstruction. This suggested that small airway wall thickening without lumen narrowing may be an early feature of airway remodeling in DETs. The effect of DE exposure status on wall area percent did not differ by lobes or smoking status. Although the trend test was of borderline significance between categorized CCAM and wall area percent, subjects in the highest CCAM category has a 14% increase in wall area percent for the 6th generation of airways compared to subjects in the lowest category. The impact of DE exposure on FEV1 can be partially explained by the wall area percent with mediation effect size equal to 20%, Pperm = 0.028). CONCLUSIONS: Small airway wall thickening without lumen narrowing may be an early image feature detected by CT and underlie the pathology of lung injury in DETs. The pattern of changes in small airway dimensions, i.e., thicker airway wall without lumen narrowing caused by occupational DE exposure was different to that (i.e., thicker airway wall with lumen narrowing) seen in our previous study of workers exposed to nano-scale carbon black aerosol, suggesting constituents other than carbon cores may contribute to such differences. Our study provides some imaging indications of the understanding of the pulmonary toxicity of combustion derived airborne particulate matters in humans.
Asunto(s)
Exposición Profesional , Emisiones de Vehículos , China , Humanos , Masculino , Exposición Profesional/estadística & datos numéricos , Material Particulado/análisis , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Pneumonia is one of the principal reasons for incidence and death in the world. The former research mainly concentrated on specific sources of patients. Besides, due to the heterogeneity among regions, there are inconsistencies in the outcome of these surveys. To explore the relationship between atmospheric pollution and hospital visits for pneumonia under the climate and pollution conditions in Qingdao, we carried out this study. METHODS: The medical records of pneumonia patients were gathered from the affiliated hospital of Qingdao University during Jan 1st, 2014, and Dec 31st,2018. Daily concentrations of PM2.5, PM10, SO2, NO2, as well as CO, were collected from the national air quality monitoring stations in Qingdao. Case-crossover study design and conditional logistic regression model were used to estimate the associations. Daily temperature, relative humidity, and atmospheric pressure were adjusted as the covariates in all models. A principal component analysis was used to solve the multicollinearity between atmospheric pollutants and investigate the relationship between various air pollutants and pneumonia occurs. RESULTS: In the single pollutant model, with interquartile range increment of the density of PM2.5, PM10, NO2 and SO2 at the lag2 days, the odds ratio of hospital visits for pneumonia patients increased by 6.4% (95%CI, 2.3-10.7%), 7.7% (95%CI, 3.2-12.4%), 6.7% (95%CI, 1.0-12.7%), and 7.2% (95%CI, 1.1-13.5%). Stratified analysis showed that pollutants were more significant in the cold period. Besides, the impact of atmospheric particulates on different ages mainly occurs in the young child (0 to 3-year-old). The odds ratio was 1.042 (95%CI, 1.012-1.072) when the principal components of atmospheric pollutants were included in the conditional logistic model. CONCLUSIONS: Our study found a significant relationship between short-term uncovering to PM2.5, PM10, NO2, SO2, and hospital visits for pneumonia in Qingdao. The effect of atmospheric pollutants mainly arose in a cold period. The particulate matter might be the principal reason in inducing hospital visits for pneumonia.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Neumonía , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Niño , Preescolar , China/epidemiología , Estudios Cruzados , Hospitales , Humanos , Lactante , Recién Nacido , Material Particulado/efectos adversos , Material Particulado/análisis , Neumonía/epidemiologíaRESUMEN
In China, studies on lead exposure to grownup are scarce compared to children, although relevant disease burdens for adults are much severe than that in developed countries. The present study evaluated blood lead levels (BLLs) in Chinese adults by data mining using Monte Carlo simulation. A total of 115 scientific studies published between January 1980 and March 2021 reflecting 45,514 Chinese adults were included in the study. After a continuous increase in Chinese adult BLLs from 1980-1983 (GM 74.84 µg/L) to 1994-1996 (GM 92.27 µg/L), BLLs began to decline from 2000--2002 (GM 80.32 µg/L) to 2016-2018 (GM 21.57 µg/L). This decline implied that the lead phase-out policy in gasoline was effective over the past two decades. The study indicated that North, South, and Southwest China were still relatively high compared to other regions in the past decade. Statistical analysis showed that BLLs of males (GM 68.45 µg/L) were higher than females (GM 56.51 µg/L), smokers (GM 80.96 µg/L) higher than nonsmokers (GM 58.95 µg/L), and populations over 40 (GM 40.43 µg/L) higher than younger populations (GM 40.37 µg/L). The significantly positive correlation between the concentrations of PM2.5 and topsoil lead and BLLs in Chinese adults indicated that air and soil pollution affect adult BLLs. Taken together, our results showed that strict lead control strategies and regular bio-monitoring are needed to maintain low BLLs in the population.
RESUMEN
Effects of heat treatment conditions (including temperature and time) on the shape memory recovery and corrosion resistance of NiTi self-expanding vascular stents were studied based on working mechanism and clinical use. The Af temperature, dimensional recovery, crush resistance with radially applied load and point applied load of stents and corrosion resistance were characterized in diffident heat treatment conditions. The research results allow the conclusion that the stent treated at 500 â for 10 min has optimum performance, and corrosion resistance meets the requirements.
Asunto(s)
Aleaciones , Calor , Corrosión , Ensayo de Materiales , Stents , Propiedades de Superficie , Temperatura , TitanioRESUMEN
BACKGROUND: Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments. RESULTS: The average elemental carbon level inside carbon black bagging facilities was 657.0 µg/m3, which was 164-fold higher than that seen in reference areas (4.0 µg/m3). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-α, IL-1ß, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses. CONCLUSIONS: Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.
Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Exposición Profesional , Hollín/toxicidad , Enfermedades Vasculares/inducido químicamente , Moléculas de Adhesión Celular/metabolismo , Humanos , Inflamación , Interleucina-1beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/metabolismoRESUMEN
Carbon black (CB) particulates as virtually pure elemental carbon can deposit deep in the lungs of humans. International Agency for Research on Cancer classified CB as a Group 2B carcinogen due to inconclusive human evidence. A molecular epidemiological study was conducted in an established cohort of CB packers (CBP) to assess associations between CB exposure and genomic instability in peripheral lymphocytes using cytokinesis-block micronucleus assay (CBMN). Carbon content in airway macrophages (CCAM) was quantified as a bio-effective dosimeter for chronic CB exposure. Dose-response observed in CBPs was compared to that seen in workers exposed to diesel exhaust. The association between CB exposure status and CBMN endpoints was identified in 85 CBPs and 106 non-CBPs from a 2012 visit and replicated in 127 CBPs and 105 non-CBPs from a 2018 visit. The proportion of cytoplasm area occupied by carbon particles in airway macrophages was over fivefold higher in current CBPs compared to non-CBPs and was associated with CBMN endpoints in a dose-dependent manner. CB aerosol and diesel exhaust shared the same potency of inducing genomic instability in workers. Circulatory pro-inflammatory factors especially TNF-α was found to mediate associations between CB exposure and CBMN endpoints. In vitro functional validation supported the role of TNF-α in inducing genomic instability. An estimated range of lower limits of benchmark dose of 4.19-7.28% of CCAM was recommended for risk assessment. Chronic CB exposure increased genomic instability in human circulation and this provided novel evidence supporting its reclassification as a human carcinogen.
Asunto(s)
Contaminantes Ocupacionales del Aire/metabolismo , Macrófagos/metabolismo , Exposición Profesional/análisis , Hollín/metabolismo , Contaminantes Ocupacionales del Aire/análisis , Contaminantes Ocupacionales del Aire/toxicidad , Humanos , Pulmón/efectos de los fármacos , Pruebas de Micronúcleos , Hollín/análisisRESUMEN
AIM: Polyhexamethylene guanidine (PHMG) is widely used as a disinfectant with broad spectra of bactericidal activity and low oral toxicity. However, inhalation of PHMG can cause pulmonary injury and severe pulmonary fibrosis. The mechanism underlying PHMG aerosol induced pulmonary fibrosis remains unclear. In this study, we aimed to examine the subchronic lung injury and determine potential cytokines involved in PHMG aerosol induced fibrosis. METHODS: C57BL/6N mice were exposed to 1.03 mg/m3 PHMG through aerosol inhalation for 3 weeks, or 3 weeks followed by other 3 weeks recovery. RESULTS: The results indicated that the expression of transforming growth factor-beta1 (TGF-ß1) and extracellular matrix remodeling markers were up-regulated in the PHMG-treated mice and these parameters were aggravated after 3 weeks recovery. Bronchoalveolar lavage fluids (BALFs) analysis showed that the number of total cells was significantly decreased in exposure group. The percentage of macrophages in BALFs decreased significantly whereas the percentage of neutrophils and lymphocytes increased. Extensive collagen deposition was observed in the peribronchiolar and interstitial areas in the PHMG exposed lungs. CONCLUSION: In conclusion, even low-does PHMG aerosol exposure could induce mice pulmonary local inflammation and irreversible fibrosis. In addition, TGF-ß/Smad signaling pathway mediated the extracellular matrix remodeling involved in the development of pulmonary fibrosis.
Asunto(s)
Desinfectantes/toxicidad , Guanidinas/toxicidad , Exposición por Inhalación/efectos adversos , Fibrosis Pulmonar/inducido químicamente , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Actinas/metabolismo , Aerosoles , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Exposición por Inhalación/análisis , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Macrófagos/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Neutrófilos/efectos de los fármacos , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Transducción de Señal , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
OBJECTIVE: To investigate the feasibility of using liquid chromatography (HPLC) to characterize the 3, 4-Dihydroxyphenylalanine (DOPA) redox state of mussel adhesive protein (MAP). METHODS: The DOPA and protein contents of MAP were determined by HPLC, Arnow and Bradford methods respectively. RESULTS: With extended oxidation time, the protein contents of MAP samples remained unchanged whereas the DOPA contents declined. The retention times of main peaks in HPLC for both the accelerated oxidation and retained samples shifted as the storage time extended, which could be related to the changes of sample redox state. CONCLUSIONS: The redox state of MAP can be characterized by the change of HPLC peak retention time. HPLC can be used in the research on the MAP redox state, which is beneficial to the product development and quality control.
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Cromatografía Liquida , Dihidroxifenilalanina , Proteínas , Dihidroxifenilalanina/química , Oxidación-ReducciónRESUMEN
As a widely used nanomaterial in daily life, silver nanomaterials may cause great concern to female reproductive system as they are found to penetrate the blood-placental barrier and gain access to the ovary. However, it is largely unknown about how silver nanomaterials influence ovarian physiology and functions such as hormone production. This study performs in vitro toxicology study of silver nanomaterials, focusing especially on cytotoxicity and steroidogenesis and explores their underlying mechanisms. This study exposes primary rat granulosa cells to gold nanorod core/silver shell nanostructures (Au@Ag NRs), and compares outcomes with cells exposed to gold nanorods. The Au@Ag NRs generate more reactive oxygen species and reduce mitochondrial membrane potential and less production of adenosine triphosphate. Au@Ag NRs promote steroidogenesis, including progesterone and estradiol, in a time- and dose-dependent manner. Chemical reactivity and transformation of Au@Ag NRs are then studied by electron spin resonance spectroscopy and X-ray absorption near edge structure, which analyze the generation of free radical and intracellular silver species. Results suggest that both particle-specific activity and intracellular silver ion release of Au@Ag NR contribute to the toxic response of granulosa cells.
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Oro/química , Nanopartículas del Metal/química , Nanoestructuras/química , Nanoestructuras/toxicidad , Nanotubos/química , Plata/química , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The interaction between bone marrow-derived mesenchymal stem cells (BDMSCs) and tumor cells promotes tumor proliferation and metastasis. We found that 4T1 breast cancer cells induced malignant differentiation of BDMSCs and that BDMSCs also affected the growth and metastasis of 4T1 cells. However, when the interaction between BDMSCs and 4T1 cells was attenuated or blocked by C60(OH)22 nanoparticles, tumor growth and metastasis were significantly suppressed. The suppression of metastasis depended on the activation of MAPK signals in the BDMSCs, whereas the underlying pathways were related to a broad range of extracellular responses and were modulated by the secretion of multiple cytokines. Interestingly, C60(OH)22 regulated the malignantly differentiated BDMSCs via the Erk- and p38-MAPK and its downstream NF-κB signal pathway, but in normal BDMSCs regulation occurred only through Erk- and p38-MAPK and not by NF-κB activation. This study may provide a novel mechanism for C60(OH)22 nanoparticles as an anti-tumor drug.
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Médula Ósea/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Fulerenos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Nanopartículas/administración & dosificación , Animales , Médula Ósea/metabolismo , Médula Ósea/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Movimiento Celular/efectos de los fármacos , Femenino , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Ratones , Ratones Endogámicos BALB C , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: The present study was designed to analysis some misunderstanding on "medical devices classification rules" of CFDA, in order to correct understand and use the regulation. METHODS: The contents of "medical devices classification rules" by CFDA have been analysis and generalized. RESULTS: Through analyzing, we can conclude as followed:the priority principle of classification catalogue; the comprehensive judgment principle based on the classification decision table and special classification principles; medical devices' management class could be changed by CFDA according to risk analysis results. CONCLUSIONS: It is helpful to reach an agreement on the classification of a medical device among the regulatory authorities, production enterprises and other aspects, and establish a solid foundation for CFDA's regulatory science.
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Equipos y Suministros/clasificación , Regulación Gubernamental , HumanosRESUMEN
Establishment of analytical methods of engineered nanomaterials in consumer products for their human and environmental risk assessment becomes urgent for both academic and industrial needs. Owing to the difficulties and challenges around nanomaterials in complex media, proper chemical separation and biological assays of nanomaterials from nanoproducts needs to be firstly developed. Herein, a facile and rapid method to separate and analyze gold nanomaterials in cosmetics is reported. Gold nanomaterials are successfully separated from different facial or eye creams and their physiochemical properties are analyzed by quantitative and qualitative state-of-the art techniques with high sensitivity or high spatial resolution. In turn, a protocol including quantification of gold by inductively coupled plasma mass spectrometry and thorough characterization of morphology, size distribution, and surface property by electron microscopes, atomic force microscope, and X-ray photoelectron spectroscope is developed. Subsequently, the preliminary toxicity assessment indicates that gold nanomaterials in cosmetic creams have no observable toxicity to human keratinocytes even after 24 h exposure up to a concentration of 200 µg mL-1 . The environmental scanning electron microscope reveals that gold nanomaterials are mostly attached on the cell membrane. Thus, the present study provides a full analysis protocol for toxicity assessment of gold nanomaterials in consumer products (cosmetic creams).
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Seguridad de Productos para el Consumidor , Cosméticos , Oro/análisis , Nanoestructuras/análisis , Medición de Riesgo , Piel/patología , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/ultraestructura , Microscopía de Fuerza Atómica , Nanoestructuras/química , Nanoestructuras/toxicidad , Tamaño de la Partícula , Espectroscopía de Fotoelectrones , Espectrometría por Rayos XRESUMEN
Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application. FROM THE CLINICAL EDITOR: The interest in the use of immunotherapy in cancer has rekindled recently. However, many approaches have shown disappointing results. In this study, the authors investigated the effects of polyhydroxylated fullerenol nanoparticles on regulating macrophages for immunotherapy. These positive findings may point a novel way to cancer treatment.
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Antineoplásicos/administración & dosificación , Fulerenos/administración & dosificación , Inmunoterapia Adoptiva , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Línea Celular Tumoral , Citocinas/biosíntesis , Fulerenos/efectos adversos , Gadolinio/química , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Nanopartículas/química , Metástasis de la Neoplasia , Neoplasias/inmunología , Neoplasias/patologíaRESUMEN
The classification messages of non-powered suction apparatus device (NPSAD) intended for negative pressure wound therapy by CFDA have been analysis and generalized. A set of classification regular patterns of NPSAD have been generalized from its intended use, composition, mechanism, contact area and resorbable characteristic. It is helpful to draw a more consistent classification in NPSAD.