Metallic nickel nano- and fine particles induce JB6 cell apoptosis through a caspase-8/AIF mediated cytochrome c-independent pathway

<p>Abstract</p> <p>Background</p> <p>Carcinogenicity of nickel compounds has been well documented. However, the carcinogenic effect of metallic nickel is still unclear. The present study investigates metallic nickel nano- and fine particle-induced apoptosis and the signal pathways involved in this process in JB6 cells. The data obtained from this study will be of benefit for elucidating the pathological and carcinogenic potential of metallic nickel particles.</p> <p>Results</p> <p>Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we found that metallic nickel nanoparticles exhibited higher cytotoxicity than fine particles. Both metallic nickel nano- and fine particles induced JB6 cell apoptosis. Metallic nickel nanoparticles produced higher apoptotic induction than fine particles. Western-blot analysis showed an activation of proapoptotic factors including Fas (CD95), Fas-associated protein with death domain (FADD), caspase-8, death receptor 3 (DR3) and BID in apoptotic cells induced by metallic nickel particles. Immunoprecipitation (IP) western blot analysis demonstrated the formation of the Fas-related death-inducing signaling complex (DISC) in the apoptotic process. Furthermore, lamin A and beta-actin were cleaved. Moreover, we found that apoptosis-inducing factor (AIF) was up-regulated and released from mitochondria to cytoplasm. Interestingly, although an up-regulation of cytochrome <it>c </it>was detected in the mitochondria of metallic nickel particle-treated cells, no cytochrome <it>c </it>release from mitochondria to cytoplasm was found. In addition, activation of antiapoptotic factors including phospho-Akt (protein kinase B) and Bcl-2 was detected. Further studies demonstrated that metallic nickel particles caused no significant changes in the mitochondrial membrane permeability after 24 h treatment.</p> <p>Conclusion</p> <p>In this study, metallic nickel nanoparticles caused higher cytotoxicity and apoptotic induction than fine particles in JB6 cells. Apoptotic cell death induced by metallic nickel particles in JB6 cells is through a caspase-8/AIF mediated cytochrome <it>c</it>-independent pathway. Lamin A and beta-actin are involved in the process of apoptosis. Activation of Akt and Bcl-2 may play an important role in preventing cytochrome <it>c </it>release from mitochondria to the cytoplasm and may also be important in the carcinogenicity of metallic nickel particles. In addition, the results may be useful as an important reference when comparing the toxicities of different nickel compounds.</p

Commuting on Public Transport: Health Risks and Responses

Rapid urbanization places a huge demand for infrastructure on busy city roads, exposing commuters to the health risks of atmospheric air pollutants. Traffic-related air pollution causes significant health burdens worldwide and enormous economic losses. Both short- and long-term exposures to atmospheric air pollutants cause a range of adverse health effects on people who commute. The short-term symptoms of exposure include coughing, shortness of breath, chest pain, and headaches. Long-term exposure is associated with cardiovascular, respiratory, and lung cancer mortality. Exposure to traffic-related air pollution also has detrimental effects on psychological and mental health. Although the use of proper respiratory protection may greatly reduce inhalation of microparticulate matter commonly found at high concentrations on busy roads, its use is not common in some communities. The adverse health risks associated with traffic-related air pollution can also be reduced through diet and lifestyle modifications, and these should be encouraged. A lack of environmental health literacy may result in the underutilization of preventive resources; therefore, fostering proper delivery of information may improve the health of commuters. Attention is drawn to the need for research tailored to individual societies or countries due to the influence of innumerable factors such as culture, religion, and climate, as well as policy and governance that contribute to diversity among health impacts and local community mitigation measures

Effects of alfalfa flavonoids extract on the microbial flora of dairy cow rumen

Objective The effect of flavonoids from alfalfa on the microbial flora was determined using molecular techniques of 16S ribosome deoxyribonucleic acid (rDNA) analysis. Methods Four primiparous Holstein heifers fitted with ruminal cannulas were used in a 4×4 Latin square design and fed a total mixed ration to which alfalfa flavonoids extract (AFE) was added at the rates of 0 (A, control), 20 (B), 60 (C), or 100 (D) mg per kg of heifer BW. Results The number of operational taxonomic units in heifers given higher levels of flavonoid extract (C and D) was higher than for the two other treatments. The Shannon, Ace, and Chao indices for treatment C were significantly higher than for the other treatments (p<0.05). The number of phyla and genera increased linearly with increasing dietary supplementation of AFE (p<0.05). The principal co-ordinates analysis plot showed substantial differences in the microbial flora for the four treatments. The microbial flora in treatment A was similar to that in B, C, and D were similar by the weighted analysis. The richness of Tenericutes at the phylum level tended to increase with increasing AFE (p = 0.10). The proportion of Euryarchaeota at the phylum level increased linearly, whereas the proportion of Fusobacteria decreased linearly with increasing AFE supplementation (p = 0.04). The percentage of Mogibacterium, Pyramidobacter, and Asteroleplasma at the genus level decreased linearly with increasing AFE (p<0.05). The abundance of Spirochaeta, Succinivibrio, and Suttonella at the genus level tended to decrease linearly with increasing AFE (0.05<p<0.10). Conclusion Including AFE in the diet of dairy cows may alter the microbial composition of the rumen; however its effect on nutrient digestibility remains to be determined

Raw Single-Wall Carbon Nanotubes Induce Oxidative Stress and Activate MAPKs, AP-1, NF-κB, and Akt in Normal and Malignant Human Mesothelial Cells

Background Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells. Objective Exposure to asbestos is the primary cause of malignant mesothelioma in 80–90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT. Methods In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor κB (NF-κB), and protein serine-threonine kinase (Akt). Results Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-κB, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure. Conclusions The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies

Ultrasound radiomics models based on multimodal imaging feature fusion of papillary thyroid carcinoma for predicting central lymph node metastasis

ObjectiveThis retrospective study aimed to establish ultrasound radiomics models to predict central lymph node metastasis (CLNM) based on preoperative multimodal ultrasound imaging features fusion of primary papillary thyroid carcinoma (PTC).MethodsIn total, 498 cases of unifocal PTC were randomly divided into two sets which comprised 348 cases (training set) and 150 cases (validition set). In addition, the testing set contained 120 cases of PTC at different times. Post-operative histopathology was the gold standard for CLNM. The following steps were used to build models: the regions of interest were segmented in PTC ultrasound images, multimodal ultrasound image features were then extracted by the deep learning residual neural network with 50-layer network, followed by feature selection and fusion; subsequently, classification was performed using three classical classifiers—adaptive boosting (AB), linear discriminant analysis (LDA), and support vector machine (SVM). The performances of the unimodal models (Unimodal-AB, Unimodal-LDA, and Unimodal-SVM) and the multimodal models (Multimodal-AB, Multimodal-LDA, and Multimodal-SVM) were evaluated and compared.ResultsThe Multimodal-SVM model achieved the best predictive performance than the other models (P &lt; 0.05). For the Multimodal-SVM model validation and testing sets, the areas under the receiver operating characteristic curves (AUCs) were 0.910 (95% CI, 0.894-0.926) and 0.851 (95% CI, 0.833-0.869), respectively. The AUCs of the Multimodal-SVM model were 0.920 (95% CI, 0.881-0.959) in the cN0 subgroup-1 cases and 0.828 (95% CI, 0.769-0.887) in the cN0 subgroup-2 cases.ConclusionThe ultrasound radiomics model only based on the PTC multimodal ultrasound image have high clinical value in predicting CLNM and can provide a reference for treatment decisions

“Caracterización de los sistemas de producción de ovinos de pelo en el suroeste del departamento de Matagalpa 2010”

Con el objetivo de caracterizar los sistemas de producción de ovinos de pelo en el territorio suroeste del departamento de Matagalpa 2010. (Sébaco, Ciudad Darío, San Isidro y Matagalpa). Se aplicó una encuesta a 103 productores que poseen ovinos de pelo, la muestra se definió aleatoriamente utilizando la ecuación planteada por Scheaffer (1987), se utilizó la técnica de muestreo de bola de nieve, planteada por Frey et al (2000). Esta investigación permitió conocer las debilidades y oportunidades en los sistemas de explotación de esta especie promisoria para la zona seca del país. Con los resultados obtenidos de las encuestas se procedió ha elaborar una base de datos en el programa SPSS versión 11.5 en español. Encontrando un predominio del sexo femenino como titulares de las explotaciones ovinas, 58.3% cursó educación primaria, el 98% de las explotaciones cuentan con raza pelibuey, el 100% de las explotaciones realizan destete y monta de forma natural, una media de mortalidad de corderos de 1, alimentan a las ovejas con potrero sin división (81.6%), se suministra pasto de corte, pastoreo, leguminosas y se suplementa sal común 49.5%, aplican vacunas contra ántrax y pierna negra (63.1%), desparasitaciones internas y externas (66%), ambos con una frecuencia de 2 veces al año, en el manejo productivo no se lleva control en la actividad ovina (100%), los equipo e instalaciones son rústicas, los corrales ovinos el son elaborados con alambre y/o madera, techado con plástico y/o zinc (49.51%), en cuanto a asistencia técnica el 58.3% ha recibid

K13 blocks KSHV lytic replication and deregulates vIL6 nad hIL6 expression: A model of lytic replication induced clonal selection in viral oncogenesis

Background. Accumulating evidence suggests that dysregulated expression of lytic genes plays an important role in KSHV (Kaposi's sarcoma associated herpesvirus) tumorigenesis. However, the molecular events leading to the dysregulation of KSHV lytic gene expression program are incompletely understood. Methodoloxy/Principal Findings. We have studied the effect of KSHV-encoded latent protein vFLIP K13, a potent activator of the NF-κB pathway, on lytic reactivation of the virus. We demonstrate that K13 antagonizes RTA, the KSHV lytic-regulator, and effectively blocks the expression of lytic proteins, production of infectious virions and death of the infected cells. Induction of lytic replication selects for clones with increased K13 expression and NF-κB activity, while siRNA-mediated silencing of K13 induces the expression of lytic genes. However, the suppressive effect of K13 on RTA-induced lytic genes is not uniform and it falls to block RTA-induced viral IL6 secretion and cooperates with RTA to enhance cellular IL-6 production, thereby dysregulating the lytic gene expression program. Conclusions/Significance. Our results support a model in which ongoing KSHV, lytic replication selects for clones with progressively higher levels of K13 expression and NF-κB activity, which in turn drive KSHV tumorigenesis by not only directly stimulating cellular survival and proliferation, but also indirectly by dysregulating the viral lytic gene program and allowing non-lytic production of growth-promoting viral and cellular genes. Lytic Replication-Induced Clonal Selection (LyRICS) may represent a general mechanism in viral oncogenesis. 2007 Zhao et al

Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

Background: With a wide range of applications, titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO2 nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. Methods: In this study, mice were injected intravenously with a single dose of TiO2 NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. Results: Death of mice in the highest dose (1387 mg/kg) group was observed at day two after TiO2 NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC) count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW) coefficients, and lower liver and kidney coefficients in the TiO2 NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO2 NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO2 NPs treated mice. Conclusions: Intravenous injection of TiO2 NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed