Use of 3D echocardiography facilitates analysis of thrombolytic efficacy in patients with persistent atrial fibrillation.

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation (AF). During follow-up after 9 to 24 weeks of Rivaroxaban treatment, patients were divided into 'effective group' (n = 143) and 'ineffective group' (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAADmean), angle between left atrial appendage and left atrial (LAA-A), velocity of blood flow in left atrial appendage (LAA-v) and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF and LAA-v values were greater and LAD and LAADmean values were lower in the effective (P<0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A and LAA-v with anticoagulant efficacy (P<0.05). The efficacy of Rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A and LAA-v. Multivariate logistic regression analysis further revealed LAEF (OR 1.7, 95% CI 0.45-16.9, P=0.008), 3D-EF (OR 6.4, 95% CI 1.06-16.9, P=0.039), and left ventricular global longitudinal strain (GLS) (OR 18.0, 95% CI 1.38-35.68, P=0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of Rivaroxaban as an anticoagulation agent.

[Deficiency of cathepsin K improves ischemic angiogenesis in high-fat diet fed mice].

The present study aims to investigate the effect of cathepsin K (CatK) on ischemic angiogenesis in high-fat diet fed mice. The mice were subjected to unilateral hindlimb ischemic surgery, and the ischemic blood flow was measured with a laser Doppler blood flow imager. Immunohistochemical staining was used to observe the quantity of new capillaries in the ischemic lower extremity, and Western blot was used to detect the expression of insulin receptor substrate-1 (IRS-1), p-Akt, Akt and vascular endothelial growth factor (VEGF). Firstly, the effect of high-fat diet on ischemic angiogenesis was observed in wild-type mice, which were randomly divided into control group and high-fat diet group and were fed with normal diet or 60% high-fat diet respectively for 16 weeks. The results showed the body weight and the plasma CatK concentration of the high-fat diet group was significantly increased compared with the control group (P < 0.05), and the blood flow recovery of the high-fat diet group was significantly lower than control group (P < 0.05). Then, wild-type and CatK knock out (CatK-/-) mice were both fed with high-fat diet to further observe the effect and mechanism of CatK on ischemic angiogenesis under high-fat diet. The results showed that the blood flow recovery in the CatK-/- group was significantly greater than the wild-type group, and the number of CD31 positive cells was significantly increased (P < 0.05). At the same time, the protein expression levels of IRS-1, p-Akt and VEGF in the ischemic skeletal muscle were significantly increased in the CatK-/- group compared with the wild-type group (P < 0.05). These results suggest that the deficiency of CatK improves ischemic angiogenesis in high-fat diet fed mice through IRS-1-Akt-VEGF signaling pathway.

Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.

Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.

Direct Photocatalytic Methane Oxidation to Formaldehyde by N Doping Co-Decorated Mixed Crystal TiO2.

In this paper, N-doped TiO2 mixed crystals are prepared via direct calcination of TiN for highly selective oxidation of CH4 to HCHO at room temperature. The structures of the prepared TiO2 samples are characterized to be N-doped TiO2 of anatase and rutile mixed crystals. The crystal structures of TiO2 samples are determined by XRD spectra and Raman spectra, while N doping is demonstrated by TEM mapping, ONH inorganic element analysis, and high-resolution XPS results. Significantly, the production rate of HCHO is as high as 23.5 mmol·g-1·h-1 with a selectivity over 90%. Mechanism studies reveal that H2O is the main oxygen source and acts through the formation of ·OH. DFT calculations indicate that the construction of a mixed crystal structure and N-doping modification mainly act by increasing the adsorption capacity of H2O. An efficient photocatalyst was prepared by us to convert CH4 to HCHO with high yield and selectivity, greatly promoting the development of the photocatalytic CH4 conversion study.

Roles of Rho/Rock signaling pathway in silica-induced epithelial-mesenchymal transition in human bronchial epithelial cells.

OBJECTIVE: To investigate the roles of Rho/Rock signaling pathway in silica-induced Epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (BEC) in vitro. METHODS: Human BEC were incubated with silica with various concentrations for indicated times. Cell viability was assayed by MTT test. Morphologic Changes were observed by microscope. Mesenchymal marker α-smooth muscle actin (α-SMA), vimentin (Vim), and epithelial marker E-cadherin (E-cad) were analyzed by Western Blot. The pull-down assay was used to measure Rho activity. In the prevention experiments, the specific inhibitor for Rho effector ROCK (Y27632) was used to inhibit the activity of Rho. RESULTS: Human BEC stimulated with silica were converted from a "cobblestone" epithelial structure into an elongated fibroblast-like shape structure. Incubation of human BEC with silica induced de novo expression of α-SMA and Vim, and loss of E-cad. Also, silica treatment resulted in Rho activation in human BEC. Y27632 up-regulated the E-cad expression but attenuated α-SMA and Vim expression in silica-stimulated cells. CONCLUSION: The activation of Rho/ROCK signaling pathways is most likely involved in Silica-induced EMT in human bronchial epithelial cells.

Crystalline metallic Au nanoparticle-loaded α-Bi2O3 microrods for improved photocatalysis.

Crystalline metallic Au nanoparticles were loaded on α-Bi(2)O(3) microrods (Au/α-Bi(2)O(3)) using an Au deposition-precipitation method. The prepared samples were characterized by scanning electron and transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectroscopy. Upon visible light irradiation, the Au/α-Bi(2)O(3) exhibits much higher photocatalytic activities than the pure α-Bi(2)O(3) for the degradation of Rhodamine B and 2,4-dichlorophenol in aqueous solution. The role of the Au and the paths of electron transport in the photocatalysis of the Au/α-Bi(2)O(3) were investigated and discussed in detail based on the analysis of the photo-generated hydroxyl radicals (˙OH) and hydrogen peroxide (H(2)O(2)) in the visible light irradiated suspension of pure α-Bi(2)O(3) and Au/α-Bi(2)O(3). The result reveals that the Au loaded on α-Bi(2)O(3) plays a critical role in the separation of the electron and hole pairs by accumulating the electrons from the excited α-Bi(2)O(3), which is responsible for the enhanced photocatalytic activity.

[Effects of Cathepsin K on spatial learning and memory in rats].

OBJECTIVE: To investigate the effects of Cathepsin K(CatK) on spatial learning and memory in rat hippocampus and its mechanisms. METHODS: Twenty male SD rats were randomly divided into Control group and CatK inhibitor group(CatKⅡ group), which were microinjected with Cathepsin K specific inhibitor(0.5 µg/µl) and artificial cerebrospinal fluid in hippocampal DG area respectively with 5 days. The cultured hippocampal neuron cells were divided into control group (CON group), negative control group(NC group), siRNA interference group(siCatK group). Three re-wells were set for each group, and samples were collected 18～20 h after siRNA transfection. Morris water maze was used to evaluate spatial learning and memory function of rats. Meanwhile, dynamic changes of glutamate(Glu) content in extracellular fluid of DG region during learning and memory were observed by microdialysis and high performance liquid chromatography in conscious rats. Western blot was used to detect CatK-mediated Notch1 activation and other signal molecules. RESULTS: Animal experiments showed that compared with the control group, the spatial learning and memory ability were decreased significantly in CatKII group, and the hippocampus protein expressions of c-Notch1, p-Akt, p-CREB and BDNF were also decreased significantly(P＜0.05); the levels of Glu in DG area of control group and CatK II group were increased significantly with Morris water maze training days, but the increase of CatK II group was significantly weaker than that of control group(P＜ 0.05). The results of cell experiment showed that the expressions of CatK, c-Notch1, p-CREB and BDNF in siCatK group were significantly lower than other groups (P＜0.05). CONCLUSION: CatK can affect the spatial learning and memory function of rats by activating Notch1 and its memory related signal protein in hippocampus.

The assembled and annotated genome of the masked palm civet (Paguma larvata).

BACKGROUND: The masked palm civet (Paguma larvata) acts as an intermediate host of severe acute respiratory syndrome coronavirus (SARS-CoV), which caused SARS, and transfered this virus from bats to humans. Additionally, P. larvata has the potential to carry a variety of zoonotic viruses that may threaten human health. However, genome resources for P. larvata have not been reported to date. FINDINGS: A chromosome-level genome assembly of P. larvata was generated using PacBio sequencing, Illumina sequencing, and Hi-C technology. The genome assembly was 2.44 Gb in size, of which 95.32% could be grouped into 22 pseudochromosomes, with contig N50 and scaffold N50 values of 12.97 Mb and 111.81 Mb, respectively. A total of 21,582 protein-coding genes were predicted, and 95.20% of the predicted genes were functionally annotated. Phylogenetic analysis of 19 animal species confirmed the close genetic relationship between P. larvata and species belonging to the Felidae family. Gene family clustering revealed 119 unique, 243 significantly expanded, and 58 significantly contracted genes in the P. larvata genome. We identified 971 positively selected genes in P. larvata, and one known human viral receptor gene PDGFRA is positively selected in P. larvata, which is required for human cytomegalovirus infection. CONCLUSIONS: This high-quality genome assembly provides a valuable genomic resource for exploring virus-host interactions. It will also provide a reliable reference for studying the genetic bases of the morphologic characteristics, adaptive evolution, and evolutionary history of this species.

[Effect of 5-hydroxymethyl furfural on BCL-2 and NF-kappaB gene expression of apoptotic rat hippocampal neurons injured by H2O2].

OBJECTIVE: To investigate the effect of 5-hydroxymethyl furfural (5-HMF) on apoptosis and BCL-2, NF-kappaB gene expression of rat hippocampal neurons injured by hydroperoxide (H2O2). METHODS: Hippocampal neurons of newly born rat were cultured in vivo and injured by H2O2. Effect of different concentration of 5-HMF on cell viability was measured by MTT. Flow cytometer (FCM) was used to measure the apoptosis of rat hippocampal neurons pre-cultured with different concentration of 5-HMF,Western blotting was used to measure the expression of BCL-2 and NF-kappaB gene. RESULTS: It revealed that the high and medium dosage of 5-HMF could increase the activity of rat hippocampal. The high, medium and low dosage of 5-HMF also increased the expression of BCL-2 gene and decreased the expression of NF-kappaB gene. CONCLUSION: 5-HMF could restrain the apoptosis of cultured hippocampal neurons injured by H2O2. The mechanism may be related to increasing in BCL-2 level and decreasing in NF-kappaB level.

[The influence of SiO2 on epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells].

OBJECTIVE: To investigate SiO2-induced EMT in human bronchial epithelial cells HBE in vitro. METHODS: HBE cells were cultured and then stimulated with indicated doses of SiO2 (0, 50, 100, 200, 300 µg/ml). The morphological changes were observed by microscope. In addition, Western blot was per-formed to detect the expression of E-cad, α-SMA and Vim. The changes of migration ability were examined by wound-healing assay in vitro. RESULTS: (1) After exposure to SiO2, HBE cells lost contact with their neighbor and displayed a spindle-shape, fibroblast-like morphology. (2) Compared with the control, the E-cad (300 µg/ml group) expression downregulated 2.98 fold (P < 0.05), and the Vim (300 µg/ml group) and α-SMA (200 µg/ml group) expression upregulated 4.46 fold and 3.55 fold (P < 0.05). There were significant differences between 100, 200, 300 µg/ml groups and the control group (P < 0.05). (3) In the test group, the percentage of wound-healing areas/wound areas were larger than those in control group (P < 0.05). CONCLUSIONS: SiO2 could induce EMT in human bronchial epithelial cells.

Transcriptome analysis reveals the genetic basis underlying the development of skin appendages and immunity in hedgehog (Atelerix albiventris).

The expression of hair features is an evolutionary adaptation resulting from interactions between many organisms and their environment. Elucidation of the mechanisms that underlie the expression of such traits is a topic in evolutionary biology research. Therefore, we assessed the de novo transcriptome of Atelerix albiventris at three developmental stages and compared gene expression profiles between abdomen hair and dorsal spine tissues. We identified 328,576 unigenes in our transcriptome, among which 4,435 were differentially expressed between hair- and spine-type tissues. Dorsal and abdomen skin tissues 5 days after birth were compared and the resulting DEGs were mainly enriched in keratin filament, epithelium cell differentiation, and epidermis development based on GO enrichment analysis, and tight junction, p53, and cell cycle signaling pathways based on KEGG enrichment analysis. MBP8, SFN, Wnt1 and KRT1 gene may involve in the development of hedgehog skin and its appendages. Strikingly, DEGs in hair-type tissues were also significantly enriched in immune-related terms and pathways with hair-type tissues exhibiting more upregulated immune genes than spine-type tissues. Our study provided a list of potential genes involved in skin appendage development and differentiation in A. albiventris, and the candidate genes provided valuable information for further studies of skin appendages.

Rational Design of Two-Dimensional Transition Metal Carbide/Nitride (MXene) Hybrids and Nanocomposites for Catalytic Energy Storage and Conversion.

Electro-, photo-, and photoelectrocatalysis play a critical role toward the realization of a sustainable energy economy. They facilitate numerous redox reactions in energy storage and conversion systems, enabling the production of chemical feedstock and clean fuels from abundant resources like water, carbon dioxide, and nitrogen. One major obstacle for their large-scale implementation is the scarcity of cost-effective, durable, and efficient catalysts. A family of two-dimensional transition metal carbides, nitrides, and carbonitrides (MXenes) has recently emerged as promising earth-abundant candidates for large-area catalytic energy storage and conversion due to their unique properties of hydrophilicity, high metallic conductivity, and ease of production by solution processing. To take full advantage of these desirable properties, MXenes have been combined with other materials to form MXene hybrids with significantly enhanced catalytic performances beyond the sum of their individual components. MXene hybridization tunes the electronic structure toward optimal binding of redox active species to improve intrinsic activity while increasing the density and accessibility of active sites. This review outlines recent strategies in the design of MXene hybrids for industrially relevant electrocatalytic, photocatalytic, and photoelectrocatalytic applications such as water splitting, metal-air/sulfur batteries, carbon dioxide reduction, and nitrogen reduction. By clarifying the roles of individual material components in the MXene hybrids, we provide design strategies to synergistically couple MXenes with associated materials for highly efficient and durable catalytic applications. We conclude by highlighting key gaps in the current understanding of MXene hybrids to guide future MXene hybrid designs in catalytic energy storage and conversion applications.

Combined proteomics and transcriptomics reveal the genetic basis underlying the differentiation of skin appendages and immunity in pangolin.

Pangolin (Mains javanica) is an interesting endangered mammal with special morphological characteristics. Here, we applied proteomics and transcriptomics to explore the differentiation of pangolin skin appendages at two developmental stages and to compare gene expression profiles between abdomen hair and dorsal scale tissues. We identified 4,311 genes and 91 proteins differentially expressed between scale-type and hair-type tissue, of which 6 genes were shared by the transcriptome and proteome. Differentiation altered the abundance of hundreds of proteins and mRNA in the two types of skin appendages, many of which are involved in keratinocyte differentiation, epidermal cell differentiation, and multicellular organism development based on GO enrichment analysis, and FoxO, MAPK, and p53 signalling pathways based on KEGG enrichment analysis. DEGs in scale-type tissues were also significantly enriched in immune-related terms and pathways compared with that in hair-type tissues. Thus, we propose that pangolins have a normal skin innate immune system. Compared with the abdomen, the back skin of pangolins had more genes involved in the regulation of immune function, which may be an adaptive adjustment for the vulnerability of scaly skin to infection and injury. This investigation provides a scientific basis for the study of development and immunity of pangolin skin, which may be helpful in the protection of wild pangolin in China.

HSP70 and mucin 5B: novel protein targets of N,N'-dinitrosopiperazine-induced nasopharyngeal tumorigenesis.

N,N'-Dinitrosopiperazine (DNP) induces nasopharyngeal carcinoma (NPC) and shows organ specificity to the nasopharyngeal epithelium. To investigate its mechanism, the rat NPC model was induced using DNP. Rat NPC and normal nasopharyngeal cells were obtained from the NPC model using laser capture. The total proteins from these cell samples were separated with two-dimension polyacrylamide gel electrophoresis techniques, and highly expressed proteins (> five-fold) were analyzed using matrix-assisted laser desorption/ionization time of flight and bioinformatics. The results showed that HSP70 and mucin 5B expression increased not only in rat NPC but also in atypical hyperplasia nasopharyngeal tissues, a precancer stage of NPC. High-expression of heat shock protein 70 (HSP70) and mucin 5B was further supported by western blot analysis. The immunofluorescence and western-blotting studies further showed that DNP induced the expression of HSP70 and mucin 5B in a dosage-dependent manner in normal nasopharyngeal epithelia cells. Our data indicate that DNP triggers over-expression of HSP70 and mucin 5B, and is involved in nasopharyngeal tumorigenesis. HSP70 and mucin 5B may be important targets in nasopharyngeal tumorigenesis induced by DNP.

Gene silencing of beta-catenin by RNAi inhibits cell proliferation in human esophageal cancer cells in vitro and in nude mice.

beta-Catenin, which is frequently overexpressed in a variety of human cancers including esophageal cancer, mediates cancer cell proliferation and tumor growth. In the present study, we used a human U6 promoter-driven DNA-template approach to induce short hairpin RNA (shRNA)-triggered RNA interference to silence beta-catenin gene expression in human esophageal squamous cell carcinoma cell line Eca-109, and then evaluated its effects on the proliferation and growth of tumor cells in vitro and in nude mice. beta-Catenin expression levels decreased markedly in Eca-109 cells transfected with a plasmid expressing shRNA for beta-catenin. Downregulation of beta-catenin was concomitantly accompanied by reduction of cyclin D1, colony formation, and growth inhibition of Eca-109 cells in vitro. The mechanism appears to be the G0/G1 phase arrest but not induction of apoptosis. In vivo, treatment of Eca-109 cells with beta-catenin shRNA greatly impeded tumor growth in nude mice. We conclude that plasmid vector-mediated beta-catenin RNA interference holds great promise as a novel treatment on human esophageal cancer with beta-catenin overexpression.

Genome Sequence of Morganella morganii DG56-16, Isolated from Shinisaurus crocodilurus.

The complete genome sequence of Morganella morganii DG56-16 was sequenced. This strain was isolated from the liver of a dead crocodile lizard (Shinisaurus crocodilurus). The genome size was 3.9 Mb, with a G+C content of 50.9%.

SMRT sequencing of the full-length transcriptome of the Sunda pangolin (Manis javanica).

It is widely known that transcriptional diversity contributes greatly to biological regulation in eukaryotes. With the development of next-generation sequencing (NGS) technologies, several studies on RNA sequencing have considerably improved our understanding of transcriptome complexity. However, obtaining full-length (FL) transcripts remains a considerable challenge because of difficulties in short read-based assembly. In the present study, single-molecule real-time (SMRT) sequencing and NGS were combined to generate the complete and FL transcriptome of Manis javanica. The results provide a comprehensive set of reference transcripts and hence contribute to the improved annotation of the M. javanica genome. We obtained 45,530 high-confidence transcripts from 19,109 genic loci, of which 8014 genes have not yet been annotated within the M. javanica genome. Furthermore, we revealed 8824 long-chain noncoding RNAs (lncRNAs). A total of 30,199 alternative splicing (AS) and 11,184 alternative polyadenylation (APA) events were identified in the sequencing data. The structure and expression level of 59 digestive enzyme genes, including 13 carbohydrase genes, 28 lipase genes and 18 protease genes, were analyzed, which might provide original data for further research on M. javanica.

[Effect of chronic iron overload on atherosclerosis lesion in apolipoprotein E knockout mice].

OBJECTIVE: To explore the effect of chronic iron overload on the lesion of atherosclerosis (AS) in apolipoprotein (apo) E knockout mice. METHODS: Twenty-four ApoE knockout mice were randomly divided into ApoE knockout group (0.1 mL saline for 4 weeks) and iron overload group (10 mg iron dextran for 4 weeks). The levels of serum iron (SI), total iron binding capacity, contents of malondialdehyde (MDA), and activity of superoxide dismutase (SOD) in the liver were measured. Iron deposition in the liver and heart was determined, and atherosclerotic plaque areas of the sinus aortae were analyzed. RESULTS: In the iron overload group, the levels of SI increased by 377.86%, the saturation of transferrin increased by 121.98% and the levels of iron in the liver increased by 2,548.15% (P<0.01). The contents of MDA in the liver increased by 32.51% (P<0.01), and the activity of SOD in the liver decreased by 17.2% in the ApoE knockout group (P<0.05). The level of MDA in the liver increased by 411.15%, and the activity of SOD in the liver decreased by 46.84% in the iron overload group (P<0.01). There was a significant deposition of iron in the liver and heart of mice, and the areas of atherosclerotic plaque of sinus aortae increased markedly in the iron overload group. CONCLUSION: Chronic iron overload may promote the development of AS lesion in the ApoE knockout mice, in which the increased oxidative stress and lipid oxidation may involve.

[Effect of Twist gene on the migration and invasion of gastric carcinoma cells].

OBJECTIVE: To explore the effect of Twist gene on the migration and invasion of human gastric carcinoma cells. METHODS: MKN28 cells, a human gastric carcinoma cell line, were transfected with PcDNA3.1-Twist plasmid by lipofectamine transfecting technique. The transfected cells were selected with geneticin. Expressions of Twist,ecadherin and vimentin protein were detected by Western blot in cells transfected Twist gene. Matrigel invision chambers were performed to analyse the cell migration and invasion. RESULTS: MKN28 cells transfected with PcDNA3.1-Twist plasmid showed stronger intracellular expression of Twist protein than MKN28 cells transfected with PcDNA3.1 and MKN28 cells without transfection. The expression of ecadherin protein in MKN28 cells transfected with PcDNA3.1-Twist plasmid was significantly decreased compared with that in MKN28 cells transfected with PcDNA3.1 and MKN28 cells without the transfection. However, The expression of vimentin protein in MKN28 cells transfected with PcDNA3.1-Twist plasmid was significantly increased compared with that in MKN28 cells transfected with PcDNA3.1 and MKN28 cells without transfection. The migration and invasion ability of Twist+ - MKN28 cells were stronger than that of MKN28 cells transfected with PcDNA3.1 and MKN28 cells without transfection. CONCLUSION: Twist gene may promote the migration and invasion ability of gastric carcinoma cells through epithelial mesenchymal transition.

[Role of activator protein-1 in pathogenesis of silicosis: an in-vitro study].

OBJECTIVE: To study the role of activator protein-1 (AP-1) in the up-regulation expression of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1(TGF-beta(1)) in silica-stimulated macrophage cells (RAW264.7). METHODS: RAW264.7 cells were treated with AP-1 inhibitor Curcumin. The expression of c-jun and c-fos in nuclear protein was detected by western blotting. The level of TNF-alpha and TGF-beta(1) protein in the cell supernatant was measured using enzyme-linked immunoadsorbent assay (ELISA). Meanwhile the expression of TNF-alpha and TGF-beta(1) mRNA was also monitored by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The nucleoprotein expression of c-jun and c-fos in 10 and 20 micromol/L Curcumin prevention group (1.150 +/- 0.020, 1.010 +/- 0.108, 80.430 +/- 0.023, 0.256 +/- 0.015) were lower than those in silica-stimulated group (1.550 +/- 0.029, 0.860 +/- 0.036) (P < 0.01). In 20 micromol/L Curcumin prevention group and silica stimulated group, the expression of TNF-alpha protein were 23.58 +/- 45.78 and 32.12 +/- 5.34, and the expression of TGF-beta(1) protein were 1582.18 +/- 437.52 and 55.60 +/- 5.51 (P < 0.05 =; the expression of TNF-alpha, TGF-beta(1) mRNA were 0.74 +/- 0.01, 0.22 +/- 0.04 and 2.27 +/- 0.33, 2.96 +/- 0.15 (P < 0.05 =. CONCLUSION: The expression of TNF-alpha, TGF-beta(1) mRNA and proteins is associated with activation of AP-1 in silica-stimulated macrophage cells.