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1.
EBioMedicine ; 51: 102603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31901862

RESUMO

BACKGROUND: Tumor necrosis factor α-induced protein 1 (TNFAIP1) is frequently downregulated in cancer cell lines and promotes cancer cell apoptosis. However, its role, clinical significance and molecular mechanisms in hepatocellular carcinoma (HCC) are unknown. METHODS: The expression of TNFAIP1 in HCC tumor tissues and cell lines was measured by Western blot and immunohistochemistry. The effects of TNFAIP1 on HCC proliferation, apoptosis, metastasis, angiogenesis and tumor formation were evaluated by Cell Counting Kit-8 (CCK8), Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), transwell, tube formation assay in vitro and nude mice experiments in vivo. The interaction between TNFAIP1 and CSNK2B was validated by liquid chromatography-tandem mass spectrometry (LC-MS/MS), Co-immunoprecipitation and Western blot. The mechanism of how TNFAIP1 regulated nuclear factor-kappaB (NF-κB) pathway was analyzed by dual-luciferase reporter, immunofluorescence, quantitative Real-time polymerase chain reaction (RT-qPCR) and Western blot. FINDINGS: The TNFAIP1 expression is significantly decreased in HCC tissues and cell lines, and negatively correlated with the increased HCC histological grade. Overexpression of TNFAIP1 inhibits HCC cell proliferation, metastasis, angiogenesis and promotes cancer cell apoptosis both in vitro and in vivo, whereas the knockdown of TNFAIP1 in HCC cell displays opposite effects. Mechanistically, TNFAIP1 interacts with CSNK2B and promotes its ubiquitin-mediated degradation with Cul3, causing attenuation of CSNK2B-dependent NF-κB trans-activation in HCC cell. Moreover, the enforced expression of CSNK2B counteracts the inhibitory effects of TNFAIP1 on HCC cell proliferation, migration, and angiogenesis in vitro and in vivo. INTERPRETATION: Our results support that TNFAIP1 can act as a tumor suppressor of HCC by modulating TNFAIP1/CSNK2B/NF-κB pathway, implying that TNFAIP1 may represent a potential marker and a promising therapeutic target for HCC.

2.
Plant Biotechnol J ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916321

RESUMO

Fruit neck length (FNL) is an important quality trait in cucumber because it directly affects its market value. However, its genetic basis remains largely unknown. We identified a candidate gene for FNL in cucumber using a next-generation sequencing-based bulked segregant analysis in F2 populations, derived from a cross between Jin5-508 (long necked) and YN (short necked). A quantitative trait locus (QTL) on chromosome 7, Fnl7.1, was identified through a genome-wide comparison of single nucleotide polymorphisms between long and short FNL F2 pools, and it was confirmed by traditional QTL mapping in multiple environments. Fine genetic mapping, sequences alignment and gene expression analysis revealed that CsFnl7.1 was the most likely candidate Fnl7.1 locus, which encodes a late embryogenesis abundant protein. The increased expression of CsFnl7.1 in long-necked Jin5-508 may be attributed to mutations in the promoter region upstream of the gene body. The function of CsFnl7.1 in FNL control was confirmed by its overexpression in transgenic cucumbers. CsFnl7.1 regulates fruit neck development by modulating cell expansion. Probably, this is achieved through the direct protein-protein interactions between CsFnl7.1 and a dynamin-related protein CsDRP6 and a germin-like protein CsGLP1. Geographical distribution differences of the FNL phenotype were found among the different cucumber types. The East Asian and Eurasian cucumber accessions were highly enriched with the long-necked and short-necked phenotypes, respectively. A further phylogenetic analysis revealed that the Fnl7.1 locus might have originated from India. Thus, these data support that the CsFnl7.1 has an important role in increasing cucumber FNL.

3.
Nat Commun ; 11(1): 83, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913275

RESUMO

Architecting grain crystallographic orientation can modulate charge distribution and chemomechanical properties for enhancing the performance of polycrystalline battery materials. However, probing the interplay between charge distribution, grain crystallographic orientation, and performance remains a daunting challenge. Herein, we elucidate the spatially resolved charge distribution in lithium layered oxides with different grain crystallographic arrangements and establish a model to quantify their charge distributions. While the holistic "surface-to-bulk" charge distribution prevails in polycrystalline particles, the crystallographic orientation-guided redox reaction governs the charge distribution in the local charged nanodomains. Compared to the randomly oriented grains, the radially aligned grains exhibit a lower cell polarization and higher capacity retention upon battery cycling. The radially aligned grains create less tortuous lithium ion pathways, thus improving the charge homogeneity as statistically quantified from over 20 million nanodomains in polycrystalline particles. This study provides an improved understanding of the charge distribution and chemomechanical properties of polycrystalline battery materials.

4.
Chemosphere ; 241: 125114, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31683445

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer. It has neurotoxicity and exposure to it causes impairment of neurodevelopment, behavior and cognition. However, the molecular mechanisms responsible for the DEHP-induced neurotoxicity are not yet clearly defined. Tumor necrosis factor-induced protein 1 (TNFAIP1) was first discovered in umbilical vein endothelial cells and was further found to be important in the progress of Alzheimer's disease. Herein we explore the mechanism of TNFAIP1 in DEHP-induced neurotoxicity with the involvement of cyclic AMP response elements binding protein (CREB) signaling pathway in a mouse neuroblastoma cell line (N2a cells). We found that exposure to DEHP induced apoptosis and downregulated the expression of brain-derived neurotrophic factor (BDNF), synaptic proteins PSD 95 and synapsin-1 while upregulated the expression of TNFAIP1 and decreased the levels of phosphorylated Akt, CaMK Ⅳ, catalytic subunits of PKA and CREB in CREB signaling pathway. Knockdown of TNFAIP1 using TNFAIP1 small interfering RNA (siRNA) expression vector prevented DEHP from inhibiting CREB pathway, thus reduced apoptosis and restored expression of BDNF, PSD 95 and synapsin-1. Our data indicate that downregulation of TNFAIP1 prevents DEHP-induced neurotoxicity via activating CREB pathway. Therefore, TNFAIP1 is a potential target for relieving the DEHP-induced neurotoxicity and related neurological disorders.

5.
Mol Ther Nucleic Acids ; 18: 954-965, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31770672

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is due to the excessive lipid accumulation within hepatocytes. Metabolic nuclear receptors (MNRs) play great roles in lipid homeostasis. We have identified a novel long noncoding RNA (lncRNA), lnc-HC, which regulates hepatocytic cholesterol metabolism through reducing Cyp7a1 and Abca1 expression. Here, we further elucidate its roles in hepatic fatty acid and triglyceride (TG) metabolism through a novel lncRNA regulatory mechanism. The most prominent target of lnc-HC identified by in vitro study is PPARγ. Further studies revealed that lnc-HC negatively regulates PPARγ at both the mRNA and protein levels and suppresses hepatocytic lipid droplet formation. Importantly, the function of lnc-HC in regulating PPARγ expression depends on modulating miR-130b-3p expression from the transcriptional to the post-transcriptional level, not through lncRNA's critical modulating patterns. In vivo, the reduction of lnc-HC expression significantly decreases miR-130b-3p expression, induces PPARγ expression, and increases TG concentration in rat livers with hyperlipidemia. These findings further help in understanding the regulatory pattern of lnc-HC in hepatic lipid metabolism and might present a possible therapeutic target for improving lipid homeostasis.

6.
Front Microbiol ; 10: 2148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620105

RESUMO

Use of biologics has been widely advocated for inflammatory diseases recently. Anti-tumor necrosis factor (TNF)-α antibody therapy is reportedly effective against ocular inflammation. However, side effects of TNF-α inhibition have been reported, particularly in the form of exacerbation of infections such as tuberculosis. Paradoxical reactions such as exacerbated inflammation are also well known. Around 20 million humans are infected with human T-cell leukemia virus type 1 (HTLV-1) globally, and this virus can cause adult T-cell leukemia, HTLV-1-associated myelopathy and HTLV-1 uveitis. As for ophthalmic concerns, it has not been identified whether anti-TNF-α antibody stimulates HTLV-1-infected cells and ocular cells to induce HTLV-1 uveitis in HTLV-1 carriers. Here we investigated the effects of anti-TNF-α antibody on ocular status under HTLV-1 infectious conditions using ocular cells and HTLV-1-infected cells in vitro. We used the ARPE-19 human retinal pigment epithelial cell line as ocular cells considered to play an important role in the blood-ocular barrier, and the MT2 HTLV-1-infected cell line. Jurkat cells were used as controls. Infliximab (IFX) was used as an anti-TNF-α antibody to achieve TNF-α inhibition. We evaluated the production of inflammatory cytokines and intercellular adhesion molecule (ICAM)-1, proliferation of ARPE-19, expression of TNF-α receptor (TNF-R) and HTLV-1 proviral DNA, and the percentage of apoptotic ARPE-19. Inflammatory cytokines such as interleukin (IL)-6, IL-8, TNF, and ICAM-1 were significantly elevated through contact between ARPE-19 and MT2. Treatment with IFX tented to inhibit TNF production, although the level of production was low, but changes in IL-6, IL-8, and ICAM-1 remained unaffected. Expression of TNFR was unaltered by IFX treatment. HTLV-1 proviral DNA was not significantly changed with treatment. No change in cell growth rate or apoptotic rate of ARPE-19 was seen with the addition of IFX. In conclusion, IFX did not exacerbate production of inflammatory cytokines, and did not affect expression of TNFR, proliferation of ARPE-19, HTLV-1 proviral load, or apoptosis of ARPE-19. These results suggest that IFX does not exacerbate HTLV-1-related inflammation in the eye and represents an acceptable treatment option under HTLV-1 infectious conditions.

7.
Front Genet ; 10: 778, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572429

RESUMO

Combination with genomic DNA is one of the important ways for microRNAs (miRNAs) to perform biological processes. However, because of lack of an experimental method, the identified genomic sites targeted by microRNA were only located in the promoter and enhancer regions. In this study, based on affinity purification of labeled biotin at the 3'-end of miRNAs, we established an efficiently experimental method to screen miRNA binding sequences in the whole genomic regions in vivo. Biotinylated miR-373 was used to test our approach in MCF-7 cells, and then Sanger and next-generation sequencing were used to screen miR-373 binding sequences. Our results demonstrated that the genomic fragments precipitated by miR-373 were located not only in promoter but also in intron, exon, and intergenic. Eleven potentially miR-373 targeting genes were selected for further study, and all of these genes were significantly regulated by miR-373. Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR-373 in MCF-7 cells while not in HeLa cells. On the whole, this is an efficient method to identify miRNA targeting sequences in the whole genome.

8.
J Synchrotron Radiat ; 25(Pt 6): 1819-1826, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407194

RESUMO

Novel developments in X-ray sources, optics and detectors have significantly advanced the capability of X-ray microscopy at the nanoscale. Depending on the imaging modality and the photon energy, state-of-the-art X-ray microscopes are routinely operated at a spatial resolution of tens of nanometres for hard X-rays or ∼10 nm for soft X-rays. The improvement in spatial resolution, however, has led to challenges in the tomographic reconstruction due to the fact that the imperfections of the mechanical system become clearly detectable in the projection images. Without proper registration of the projection images, a severe point spread function will be introduced into the tomographic reconstructions, causing the reduction of the three-dimensional (3D) spatial resolution as well as the enhancement of image artifacts. Here the development of a method that iteratively performs registration of the experimentally measured projection images to those that are numerically calculated by reprojecting the 3D matrix in the corresponding viewing angles is shown. Multiple algorithms are implemented to conduct the registration, which corrects the translational and/or the rotational errors. A sequence that offers a superior performance is presented and discussed. Going beyond the visual assessment of the reconstruction results, the morphological quantification of a battery electrode particle that has gone through substantial cycling is investigated. The results show that the presented method has led to a better quality tomographic reconstruction, which, subsequently, promotes the fidelity in the quantification of the sample morphology.

9.
Int J Mol Sci ; 19(7)2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30041403

RESUMO

Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/ß-Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/ß-Catenin and NFκB signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of ß-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-α-induced NFκB activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-α-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/ß-Catenin and NFκB signaling pathway through regulating Dishevelled-1.


Assuntos
Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Proteínas Desgrenhadas/metabolismo , Globinas/genética , Humanos , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/genética , Neuroglobina , Ligação Proteica , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
10.
Nat Commun ; 9(1): 2810, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30022082

RESUMO

Redox phase transformations are relevant to a number of metrics pertaining to the electrochemical performance of batteries. These phase transformations deviate from and are more complicated than the conventional theory of phase nucleation and propagation, owing to simultaneous changes of cationic and anionic valence states as well as the polycrystalline nature of battery materials. Herein, we propose an integrative approach of mapping valence states and constructing chemical topographies to investigate the redox phase transformation in polycrystalline layered oxide cathode materials under thermal abuse conditions. We discover that, in addition to the three-dimensional heterogeneous phase transformation, there is a mesoscale evolution of local valence curvatures in valence state topographies. The relative probability of negative and positive local valence curvatures alternates during the layered-to-spinel/rocksalt phase transformation. The implementation of our method can potentially provide a universal approach to study phase transformation behaviors in battery materials and beyond.

11.
J Synchrotron Radiat ; 25(Pt 4): 1222-1228, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29979185

RESUMO

Grating-based X-ray differential phase-contrast imaging has attracted a great amount of attention and has been considered as a potential imaging method in clinical medicine because of its compatibility with the traditional X-ray tube source and the possibility of a large field of view. Moreover, phase-contrast computed tomography provides three-dimensional phase-contrast visualization. Generally, two-dimensional information retrieval performed on every projection is required prior to three-dimensional reconstruction in phase-contrast computed tomography. In this paper, a three-dimensional information retrieval method to separate absorption and phase information directly from two reconstructed images is derived. Theoretical derivations together with numerical simulations have been performed to confirm the feasibility and veracity of the proposed method. The advantages and limitations compared with the reverse projection method are also discussed. Owing to the reduced data size and the absence of a logarithm operation, the computational time for information retrieval is shortened by the proposed method. In addition, the hybrid three-dimensional images of absorption and phase information were reconstructed using an absorption reconstruction algorithm, hence the existing data pre-processing methods and iterative reconstruction algorithms in absorption reconstruction may be utilized in phase reconstruction immediately.

12.
Acc Chem Res ; 51(10): 2484-2492, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29889493

RESUMO

Functional materials and devices are usually morphologically complex and chemically heterogeneous. Their structures are often designed to be hierarchical because of the desired functionalities, which usually require many different components to work together in a coherent manner. The lithium ion battery, as an energy storage device, is a very typical example of this kind of structure. In a lithium ion battery, the cathode, anode, and separator are soaked in a liquid electrolyte, facilitating the back and forward shuttling of the lithium ions for energy storage and release. The desired performance of a lithium ion battery has many different aspects that need to be engineered and balanced depending on the targeted applications. In most cases, the cathode material has become the limiting factor for further improvements and, thus, has attracted intense attention from the research community. While the improvement in the overall performance of the lithium ion battery is the ultimate goal of the research in this field, understanding the relationship between the microscopic properties and the macroscopic behaviors of the materials/devices can inform the design of better battery chemistries for practical applications. As a result, it is of great fundamental and practical importance to investigate the electrode materials using experimental probes that can provide good chemical sensitivity and sufficient spatial resolution, ideally, under operating conditions. With this motivation, our group has been focusing on the development of the nanoscale full-field X-ray spectro-microscopy, which has now become a well-recognized tool for imaging battery electrode materials at the particle level. With nanoscale spatial resolution, this technique can effectively and efficiently tackle the intrinsically complicated mesoscale chemistry. It allows us to monitor the particles' morphological and chemical evolution upon battery operation, providing valuable insights that can be incorporated into the design of new battery chemistries. In this Account, we review a series of our recent studies of battery electrode materials using nanoscale full-field X-ray spectro-microscopy. The materials that are the subjects of our studies, including layer-structured and spinel-structured oxide cathodes, are technically very important as they not only play an important role in today's devices but also possess promising potential for future developments. We discuss how the subparticle level compositional and state-of-charge heterogeneity can be visualized and linked to the bulk performance through systematic quantification of the imaging data. Subsequently, we highlight recent ex situ and in situ observations of the cathode particles' response to different reaction conditions, including the spontaneously adjusted reaction pathways and the morphological changes for the mechanical strain release. The important role of surface chemistry in the system is also discussed. While the microscopic investigation at the particle level provides useful insights, the degree to which this represents the overall properties of the battery is always a question for further generalizing the conclusions. In order to address this concern, we finally discuss a high throughput experimental approach, in which a large number of cathode particles are scanned. We discuss a case study that demonstrates the identification and analysis of functionally important minority phases in an operating battery cell through big data mining methods. With an emphasis on the data/information mining aspect of the nanoscale X-ray spectro-microscopic study of battery cathode particles, we anticipate that this Account will attract more research to this field.

13.
ACS Nano ; 12(5): 4946-4958, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29689158

RESUMO

Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide (TiO2), as a radio-sensitizer for radiation therapy of triple-negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DAT uptake for a radio-sensitized radiation therapy.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Radiossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Titânio/química , Neoplasias de Mama Triplo Negativas/radioterapia , Animais , Apoptose , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Humanos , Camundongos Nus , Transplante de Neoplasias , Polietilenoglicóis/química , Radiossensibilizantes/uso terapêutico , Distribuição Tecidual , Neoplasias de Mama Triplo Negativas/metabolismo
14.
Rev Sci Instrum ; 88(8): 085102, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28863686

RESUMO

Grating-based X-ray phase contrast imaging technology is one of the most potential imaging methods in real applications. It can be classified into two categories: interferometry and non-interferometric imaging. The non-interferometric grating-based X-ray phase contrast imaging (NIGPCI) instrument has a great advantage in the forthcoming commercial applications for the flexible system design and the use of large periodic gratings. The performance of the NIGPCI instrument depends on its angular sensitivity to a great extent. Therefore, good angular sensitivity is mandatory in order to obtain high quality phase-contrast images. Several parameters, such as the X-ray spectrum, the inter-grating distances, and the parameters of the three gratings, influence the angular sensitivity of the imaging system. However, the quantitative relationship between the angular sensitivity and grating duty cycle is unclear. Therefore, this paper is devoted to revealing their internal relation by theoretical deduction and emulation of the imaging process with the theories of linear system and Fourier optics. Furthermore, a quantitative analysis method to optimize the duty cycles of gratings is proposed and its applicability to a general NIGPCI system is verified.

15.
Toxicol Appl Pharmacol ; 324: 36-44, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28373009

RESUMO

Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3mg/m3 FA for 2weeks, mimicking occupational exposure, and were monitored for another 7days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrow cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk.


Assuntos
Benzeno/toxicidade , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Formaldeído/toxicidade , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Animais , Benzeno/administração & dosagem , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Formaldeído/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Espécies Reativas de Oxigênio/metabolismo
16.
J Synchrotron Radiat ; 24(Pt 2): 490-497, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28244445

RESUMO

Computed tomography (CT) has become an important technique for analyzing the inner structures of material, biological and energy fields. However, there are often challenges in the practical application of CT due to insufficient data. For example, the maximum rotation angle of the sample stage is limited by sample space or image reconstruction from the limited number of views required to reduce the X-ray dose delivered to the sample. Therefore, it is difficult to acquire CT images with complete data. In this work, an iterative reconstruction algorithm based on the minimization of the image total variation (TV) has been utilized to develop equally sloped tomography (EST), and the reconstruction was carried out from limited-angle, few-view and noisy data. A synchrotron CT experiment on hydroxyapatite was also carried out to demonstrate the ability of the TV-EST algorithm. The results indicated that the new TV-EST algorithm was capable of achieving high-quality reconstructions from projections with insufficient data.

17.
Arch Toxicol ; 91(2): 921-933, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27339418

RESUMO

Formaldehyde (FA) is a human leukemogen and is hematotoxic in human and mouse. The biological plausibility of FA-induced leukemia is controversial because few studies have reported FA-induced bone marrow (BM) toxicity, and none have reported BM stem/progenitor cell toxicity. We sought to comprehensively examine FA hematoxicity in vivo in mouse peripheral blood, BM, spleen and myeloid progenitors. We included the leukemogen and BM toxicant, benzene (BZ), as a positive control, separately and together with FA as co-exposure occurs frequently. We exposed BALB/c mice to 3 mg/m3 FA in air for 2 weeks, mimicking occupational exposure, then measured complete blood counts, nucleated BM cell count, and myeloid progenitor colony formation. We also investigated potential mechanisms of FA toxicity, including reactive oxygen species (ROS) generation, apoptosis, and hematopoietic growth factor and receptor levels. FA exposure significantly reduced nucleated BM cells and BM-derived colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E); down-regulated GM-CSFRα and EPOR expression; increased ROS in nucleated BM, spleen and CFU-GM cells; and increased apoptosis in nucleated spleen and CFU-GM cells. FA and BZ each similarly altered BM mature cells and stem/progenitor counts, BM and CFU-GM ROS, and apoptosis in spleen and CFU-GM but had differential effects on other end points. Co-exposure was more potent for several end points. Thus, FA is toxic to the mouse hematopoietic system, including BM stem/progenitor cells, and it enhances BZ-induced toxic effects. Our findings suggest that FA may induce BM toxicity by affecting myeloid progenitor growth and survival through oxidative damage and reduced expression levels of GM-CSFRα and EPOR.


Assuntos
Benzeno/efeitos adversos , Células da Medula Óssea/efeitos dos fármacos , Formaldeído/toxicidade , Células-Tronco Hematopoéticas/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Contagem de Células Sanguíneas , Células da Medula Óssea/patologia , Caspase 3/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Receptores de Fatores de Crescimento/metabolismo , Baço/efeitos dos fármacos , Testes de Toxicidade/métodos
18.
PLoS One ; 11(7): e0159479, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27467143

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has an adjuvant effect in combination with ovalbumin (OVA). The adjuvant effect of DEHP has already been verified in our previous studies. In this study, to further investigate whether thymic stromal lymphopoietin (TSLP) was involved in the DEHP-adjuvant effect, DEHP was administered through a daily gavage exposure route. Mice were sensitized with ovalbumin (OVA) to trigger allergic responses, and an anti-TSLP monoclonal antibody was used to neutralize the effect of TSLP. Biomarkers including cytokines in bronchoalveolar lavage fluid (BALF), serum total IgE and TSLP content in the lung were detected. In addition, airway hyperreactivity and lung sections were examined. Collectively, these data indicated a salient Th2 response which was characterized by the upregulation of Th2-type cytokines, such as interleukin 4 (IL-4), IL-5 and IL-13. Moreover, the eosinophil number in BALF and the eosinophil cationic protein (ECP) in the lung were seen to have increased significantly. However, neutralization of TSLP with an anti-TSLP mAb reversed the adjuvant effect of DEHP on airway inflammation, structural alterations in the airway wall and increased airway hyperresponsiveness (AHR) to methacholine induced by the OVA allergen, suggesting that TSLP was an effective target site for suppressing the adjuvant effect of DEHP co-exposure.


Assuntos
Adjuvantes Imunológicos/farmacologia , Asma/imunologia , Citocinas/imunologia , Dietilexilftalato/farmacologia , Modelos Animais de Doenças , Testes de Neutralização , Animais , Líquido da Lavagem Broncoalveolar , Imunoglobulina G/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem
19.
Environ Toxicol Pharmacol ; 45: 265-73, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27343751

RESUMO

Formaldehyde and benzene are the two major indoor air pollutants due to their prevalence and toxicity. This study aimed to explore the toxic effect on the spleen and relevant immune responses of Balb/c mice caused by exposure to a combination of formaldehyde and benzene. Balb/c mice were divided randomly into five groups (n=9/group): blank control group (Ctrl); solvent ([corn] Oil) control; formaldehyde only (FA, 3mg/m(3)); benzene only (BZ, 150mg/kg BW); and, formaldehyde+benzene group (FA+BZ). Exposures were performed for 8h/day, 5 day/week, for 2 weeks. Tail blood was collected after the final exposure; 24-h later, the mice were euthanized to permit assessment of a variety of immune endpoints. The endpoints' three areas were: (1) in living mice, body weight and delayed-type hypersensitivity (DTH) responses; (2) in blood, immune cell counts and serum antibody levels (serum hemagglutination); and, (3) in spleen samples, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), caspase-3 (cell apoptosis) levels and lymphocyte proliferation. In this study we fund (1) BZ and FA+BZ exposure can lead to the reduction in the number of some immune cells in peripheral blood; (2) Formaldehyde has certain synergistic effects on benzene-induced cytotoxicity in peripheral blood, (3) FA, BZ and FA+BZ exposure can lead to ROS and GSH depletion in spleen cells, and spleen cell apoptosis (caspase-3 increased) may be one of the downstream events, decreased splenic lymphocyte proliferation; and (4) the FA+BZ combined exposure can lead to the decreased body weight, serum antibody level (by serum hemagglutination assay).


Assuntos
Poluentes Atmosféricos/toxicidade , Benzeno/toxicidade , Formaldeído/toxicidade , Leucócitos Mononucleares/efeitos dos fármacos , Baço/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Sinergismo Farmacológico , Glutationa/metabolismo , Exposição por Inalação , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Masculino , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/metabolismo , Baço/citologia , Baço/imunologia
20.
Toxicol Mech Methods ; 26(2): 75-81, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26400731

RESUMO

Formaldehyde (FA) is an environmental pollutant and an endogenous product believed to be involved in tumorigenesis. However, the underlying mechanism of observed FA effects has not been clearly defined. Paxillin is a focal adhesion protein that may play an important role in several signaling pathways. Many paxillin-interacting proteins are involved in the regulation of actin cytoskeleton organization, which is necessary for cell motility events associated with diverse biological responses, such as embryonic development, wound repair and tumor metastasis. P53 is important in multicellular organisms, where it regulates the cell cycle and thus functions as a tumor suppressor that is involved in preventing cancer. In this study, we investigated the effects of FA on paxillin-tyrosine phosphorylation and P53 expression in Hela cells by Western blot and immunofluorescence. Western blot analysis revealed that nonlethal concentrations of FA (0.5, 1.0 and 2.0 mM, with the exposure time for 0.5, 1.0 and 2.0 h, respectively) had downregulated paxillin and wild-type p53 genes expression while upregulated paxillin-tyrosine phosphorylation significantly. At the same time, phosphotyrosine at the focal adhesion sites detected by immunofluorescence assay obviously increased in Hela cells incubated with 2.0 mM FA for 2 h. The results suggested that paxillin and p53 genes expression may be involved in FA-related adverse effects and the mechanism may be involved in paxillin-tyrosine phosphorylation.


Assuntos
Poluentes Ambientais/toxicidade , Formaldeído/toxicidade , Paxilina/metabolismo , Proteína Supressora de Tumor p53/genética , Tirosina/metabolismo , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo , Células HeLa , Humanos , Paxilina/genética , Fosforilação
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