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Cr2O3 scale growth and volatilization are the main cause of the performance degradation of solid oxide fuel cells (SOFCs) with an Fe-based ferritic stainless steel (FSS) interconnect. In this work, an amorphous Ti(Nb)-Si-C coating is prepared on the pre-oxidized SUS430 with D.C. magnetron sputtering as the protective coating. The amorphous Ti(Nb)-Si-C coated alloy exhibits significantly enhanced oxidation resistance, and the oxidation kinetics obey the parabolic law with a low parabolic rate of 9.36 × 10-15 g2·cm-4·s-1. A dual-layer oxide scale is formed composed of an inner layer rich in Cr2O3 and an outer layer rich in rutile TiO2 and amorphous SiO2. MnCr2O4 appears at the interface between the inner and outer oxide layers. Meanwhile, the amorphous Ti(Nb)-Si-C coating also effectively blocks the outward diffusion of Cr. In addition, the coated steel presents good electrical properties with an area-specific resistance (ASR) of 13.57 mΩ·cm2 at 800 °C after oxidation at 800 °C in air for 500 h.
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Hydroxychloroquine (HCQ) is an autophagy inhibitor that has been used for the treatment of many diseases, such as malaria, rheumatoid arthritis, systemic lupus erythematosus, and cancer. Despite the therapeutic advances in these diseases, the underlying mechanisms have not been well determined and hinder the rational use of this drug in the future. Here, we explored the possible mechanisms and identified the potential binding targets of HCQ by performing quantitative proteomics and thermal proteome profiling on MIA PaCa-2 cells. This study revealed that HCQ may exert its functions by targeting some autophagy-related proteins such as ribosyldihydronicotinamide dehydrogenase (NQO2) and transport protein Sec23A (SEC23A), or regulating the expression of galectin-8 (LGALS8), mitogen-activated protein kinase 8 (MAPK8), and so on. Furthermore, HCQ may prevent the progression of pancreatic cancer by regulating the expression of nesprin-2 (SYNE2), protein-S-isoprenylcysteine O-methyltransferase (ICMT), and cotranscriptional regulator FAM172A (FAM172A). Together, these findings not only identified potential binding targets for HCQ but also revealed the non-canonical mechanisms of HCQ that may contribute to pancreatic cancer treatment.
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Antirreumáticos , Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Neoplasias Pancreáticas , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Galectinas , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas/uso terapêutico , ProteômicaRESUMO
Modulating the microenvironment of single-metal active sites holds excellent promises for developing highly efficiently oxygen electrocatalysts. Herein, by combining theoretical predictions and experiments, we reported a general strategy to engineer the electronic properties of iron-nitrogen-carbon (FeN4/C) catalysts via the incorporation of the boron (B) atom for achieving improved catalytic activity in oxygen electrocatalysis. Our theoretical results revealed that B modulation effectively tunes the d-band center of the iron (Fe) active site to optimize its adsorption strength with oxygenated species, greatly enhancing oxygen reduction reaction (ORR) and oxygen evolution reactions (OER) activity. Our experimental measurements then confirmed the above theoretical predictions: the as-synthesized B-doped FeN4/C (Fe-N4-B) material can perform as an eligible bifunctional catalyst for ORR and OER in alkaline media, and its catalytic activity even outperforms the commercial noble metal benchmarks. The present findings provide a promising strategy to further design the advanced catalysts for a wide range of electrochemical applications.
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The intracellular O2-supply not only can relieve tumor hypoxia but also enhance the effects of photodynamic therapy (PDT). In this work, metallic Mo2C@N-carbon@PEG nanoparticles were constructed to reveal the near infrared (NIR)-photocatalytic O2 generation and promote photodynamic therapy (PDT). Here, (NH4)6Mo7O24·4H2O nanorods and urea were adopted as resources that were calcined to obtain Mo2C@N-carbon nanoparticles (20â¯nm). All samples displayed high NIR absorption as well as photothermal conversion efficiency of up to 52.7 % (Mo2C@N-Carbon-3@PEG). The density functional theory calculations demonstrated the metallic characteristic of Mo2C and that the consecutive interband/intraband charge-transition was responsible for the high NIR harvest and redox ability of electron-hole pairs, making the NIR-photocatalytic O2 and reactive oxygen species (ROS) generation. In comparison with the pure Mo2C, the heterostructure displayed twice the performance due to the enhanced charge-segregation between Mo2C and N-carbon. Given the high X-ray absorption coefficient and photothermal ability, the nanocomposite could be used in novel computer tomography and photothermal imaging contrast. Furthermore, the novel biodegradation and metabolism behaviors of nanocomposites were investigated, which were reflected as elimination from the body (mouse) via feces and urine within 14â¯days. The as-synthesized Mo2C@N-Carbon@PEG nanocomposites integrated the dual-model imaging, intracellular O2-supply, and phototherapy into one nanoplatform, revealing its potential for anti-cancer therapy.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Carbono , Linhagem Celular Tumoral , Camundongos , Molibdênio , Neoplasias/tratamento farmacológico , Oxigênio , FototerapiaRESUMO
The development of nanotheranostic agent with imaging-guided highly therapeutic efficiency has attracted most attentions on tumor treatment. Herein, the novel MoSe2/Bi2Se3 nanosheets were designed to integrate CT/photothermal (PT) imaging and photodynamic/photothermal/chemo-therapy (PTT/PDT/chemotherapy) into one nanoplatform. Firstly, the MoSe2 nanosheets (5-30â¯nm) were prepared via ultrasound-assisted exfoliated method, and then by a cation-exchange strategy the novel sandwich nanostructure Bi2Se3/MoSe2/Bi2Se3 (Bi-M-3) were obtained, revealing the narrower band gap (1.17â¯eV) and the stronger near-infrared (NIR) absorption. Both experimental and density functional theory (DFT) calculations reveal the Z-scheme mechanism of charge transfer in the heterostructure, which induces the enhanced ROS (â OH) generation due to the efficient separation of photogenerated electron-hole pairs. Meanwhile, the nanoheterostructure also makes sure the improved photothermal conversion efficiency (59.3%). Besides, we also found the photothermal effect can promote the transfer photo-generated electron that is in favor of ROS generation. Furthermore, because of the higher absorption coefficient of X-ray for Bi atom, the heterostructure also exhibits the higher CT imaging contrast than pure MoSe2 sample. After the loading of anticancer drug Doxorubicin (Dox), Bi-M-3@PEG-Dox displays the acid/photothermal sensitive drug release behavior. The synergistic effect of chemotherapy, photodynamic and photothermal therapy further induces the superior cancer cell apoptosis and enhanced antitumor effect.
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Hipertermia Induzida , Molibdênio/química , Nanopartículas/química , Neoplasias/terapia , Compostos Organosselênicos/química , Fotoquimioterapia , Fototerapia , Tomografia Computadorizada por Raios X , Animais , Bismuto , Terapia Combinada , Células Hep G2 , Humanos , Camundongos , Imagem Multimodal , Nanopartículas/ultraestrutura , Neoplasias/patologia , Compostos de Selênio , Espectrofotometria UltravioletaRESUMO
BACKGROUND: Cryopreservation in dimethyl sulfoxide and storage at -80 °C extends the shelf life of platelets to at least 2 years, allowing greater availability in rural and military areas. While cryopreserved platelets (CPPs) have been extensively characterized for coagulation and thrombin generation, reports on the mechanism of adverse reactions to CPPs transfusion are scarce. Here, we tested the hypothesis that CPPs facilitate phagocytosis by Kupffer cells and subsequently promote the inflammatory response in Kupffer cells. STUDY DESIGN AND METHODS: P-selectin expression, glycoprotein Ibα clustering and phosphatidylserine (PS) surface exposure on platelets stored at 22 °C, 4 °C and - 80 °C for 3 days were examined by flow cytometry. The phagocytosis of mepacrine-labeled platelets coincubated with THP-1 cells was examined by flow cytometry and confocal microscopy, and the release of cytokines from THP-1 cells was measured by enzyme-linked immunosorbent assay. RESULTS: CPPs showed a marked enhancement of exposed PS but dramatically reduced glycoprotein Ibα expression and clustering compared with platelets stored at 4 °C. Activation of THP-1 cells was stronger by CPPs than by platelets stored at 22 °C and 4 °C. CPP interference tests using annexin V and anti-P-selectin showed that CPPs induced increases in PS- and P-selectin-mediated phagocytosis, as well as secretion of the proinflammatory cytokine tumor necrosis factor-α, and interleukins IL-1ß and IL-6, but a decrease in transforming growth factor-ß production in THP-1 cells. Surface-exposed PS was more effective than P-selectin for the activation of THP-1 cells. CONCLUSION: CPPs triggered PS and P-selectin-mediated phagocytosis by macrophages and stimulated the inflammatory response of macrophages.
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Plaquetas/citologia , Plaquetas/metabolismo , Criopreservação/métodos , Inflamação/metabolismo , Selectina-P/metabolismo , Fosfatidilserinas/metabolismo , Linhagem Celular , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Fagocitose/fisiologia , Complexo Glicoproteico GPIb-IX de Plaquetas/química , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , QuinacrinaRESUMO
BACKGROUND: Platelets are essential for primary hemostasis and also play an important role in inflammatory reactions. The hemostatic property of cryopreserved platelets (CPPs) has been confirmed in the treatment of bleeding casualties, but inflammatory injury induced by CPP transfusion is relatively unclear. We aim to investigate the effects of CPP transfusion on inflammatory organ injury in mice after hemorrhage. METHODS: Mice were subjected to a volume-controlled hemorrhage over 1 hour, and then were transfused with fresh platelets (FPs), Liquid-stored platelets (LPPs), CPPs, or fresh frozen plasma (FFP, control). At 6 hours posttransfusion, mice were sacrificed, and blood and tissues were sampled. Tissue sections were examined histologically and by immunohistochemical staining of neutrophils and macrophages. Plasma alanine aminotransferase, hepatic myeloperoxidase activity and inflammatory cytokine levels were measured. RESULTS: Transfusion of stored platelets (LPPs and CPPs) caused more serious histological injury in liver and lung compared with FPs and FFP (p < 0.05). However, kidney histological injury was similar among groups. Significantly higher numbers of Ly-6G-positive neutrophils were detected in liver and of F4/80-positive macrophages in liver and lung of mice transfused with LPPs or CPPs compared with FPs or FFP (p < 0.05). Transfusion of CPPs caused the most severe inflammatory liver injury, as reflected by alanine aminotransferase levels, hepatic macrophage infiltration, and hepatic myeloperoxidase activity and inflammatory cytokine levels (macrophage inflammatory protein-2, tumor necrosis factor-α, and interleukin-1ß). CONCLUSION: Cryopreserved platelet transfusion is more likely to aggravate hemorrhage-induced liver and lung injury by activating macrophage and facilitating neutrophil infiltration into hepatic tissues.
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Criopreservação , Hemorragia/terapia , Insuficiência de Múltiplos Órgãos/etiologia , Plasma , Transfusão de Plaquetas/efeitos adversos , Alanina Transaminase/sangue , Animais , Citocinas/sangue , Modelos Animais de Doenças , Hemorragia/complicações , Inflamação/patologia , Fígado/fisiopatologia , Pulmão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Hemorrhagic shock/resuscitation involves overwhelming reactive oxygen species (ROS) that cause oxidative stress, inflammation, and subsequent tissue injury. We investigated the effects of the potent antioxidant carboxyfullerene (C3) on acute liver injury during hemorrhage shock/resuscitation. C3 infusion reduced the alanine aminotransferase (ALT) activity, methemoglobin content, malondialdehyde content, myeloperoxidase activity and expression levels of tumor necrosis factor -α and interleukin-6; it increased superoxide dismutase activity in the liver. The histologic injury score and apoptotic index were also markedly decreased after C3 treatment compared with the vehicle group. Additionally, C3-treated rats showed a significant decrease in nuclear factor-κB DNA binding capacity, which was preceded by reduced phosphorylation of the nuclear factor κB (NF-κB) p65 subunit in the liver. C3 nanoparticles ameliorate oxidative stress, the inflammatory response, and subsequent acute liver injury after hemorrhagic shock/resuscitation. These protective effects appear to be mediated through the inhibition of the nuclear factor-κB pathway. C3 treatment may be a promising strategy to improve tissue injury in hemorrhagic shock/resuscitation.
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Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Ácidos Carboxílicos/administração & dosagem , Nanopartículas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Lesão Pulmonar Aguda/etiologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Ácidos Carboxílicos/química , Masculino , Nanopartículas/química , Nanopartículas/ultraestrutura , Ratos , Ratos Wistar , Choque Hemorrágico/complicações , Resultado do TratamentoRESUMO
RBCs undergo numerous changes during storage and stored RBCs may induce adverse effects, ultimately resulting in organ injury in transfusion recipients. We tested the hypothesis that the addition of SP to stored RBCs would improve the quality of the stored RBCs and mitigate liver injury after transfusion in a murine model. RBCs were harvested from C57BL/6J mice and stored for 14 days in CPDA-1 containing either a solution of SP in saline or saline alone. Haemolysis, the 24-hour posttransfusion recovery, the oxygen-carrying capacity, and the SOD activity of stored RBCs were evaluated. The plasma biochemistry, hepatic MDA level, MPO activity, IL-6, TNF-α concentrations, and histopathology were measured two hours after the transfusion of stored RBCs. Compared with RBCs stored in CPDA-1 and saline, the addition of SP to stored RBCs restored their oxygen-carrying capacity and SOD activity, reduced the AST activity, BUN concentrations, and LDH activity in the plasma, and decreased the MDA level, MPO activity, and concentrations of IL-6 and TNF-α in the liver. These data indicate that the addition of SP to RBCs during storage has a beneficial effect on storage lesions in vitro and subsequently alleviates liver injury after the transfusion of stored RBCs in vivo.
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Transfusão de Sangue/métodos , Eritrócitos/efeitos dos fármacos , Hepatopatias/terapia , Ácido Pirúvico/farmacologia , Sódio/farmacologia , Animais , Preservação de Sangue , Modelos Animais de Doenças , Hemoglobinas/química , Humanos , Interleucina-6/sangue , Ácido Láctico/sangue , Hepatopatias/patologia , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/química , Peroxidase/sangue , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS. METHODS: Rats were subjected to HS, and on resuscitation, the rats were randomly assigned to four groups (n = 8): the normoxic, the hyperoxic, the hypoxemic, and the GIOA groups. Rats were observed for an additional 1 h. Hemodynamics, acid-base status, oxygenation, and oxidative injury were observed and evaluated. RESULTS: Central venous oxygen saturation promptly recovered only in the hyperoxic and the GIOA groups, and the liver tissue partial pressure of oxygen was highest in the GIOA group after resuscitation. Oxidative stress in GIOA group was significantly reduced compared with the hyperoxic group as indicated by the reduced malondialdehyde content, increased catalase activity, and the lower histologic injury scores in the liver. In addition, the tumor necrosis factor-α and interleukin-6 expressions in the liver were markedly decreased in the GIOA group than in the hyperoxic and normoxic groups as shown by the immunohistochemical staining. CONCLUSIONS: GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation.
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Estresse Oxidativo/efeitos dos fármacos , Oxigênio/administração & dosagem , Ressuscitação/métodos , Índice de Gravidade de Doença , Choque Hemorrágico/terapia , Animais , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Ressuscitação/efeitos adversos , Choque Hemorrágico/metabolismoRESUMO
BACKGROUND: We aimed to evaluate the effects of resuscitation with different ratios of fresh frozen plasma (FFP) to red blood cells (RBCs) on pulmonary inflammatory injury and to illuminate the beneficial effects of FFP on lung protection compared with lactated ringers (LR) using a rat model of hemorrhagic shock. METHODS: Rats underwent pressure-controlled hemorrhage for 60 minutes and were then transfused with LR for initial resuscitation. Thereafter, the rats were transfused with varying ratios of FFP:RBC (1:4, 1:2, 1:1, and 2:1) or LR:RBC (1:1) to hold their mean arterial pressure (MAP) at 100 ± 3 mm Hg for 30 minutes. After 4 hours of observation, lung tissue was harvested to determine the wet/dry weight, myeloperoxidase levels, tumor necrosis factor α levels, macrophage inflammatory protein 2 (MIP-2) levels, inducible nitric oxide synthase activity, and the nuclear factor κB p65 DNA-binding activity. RESULTS: With an increase in the FFP:RBC ratio, the volume of required RBC to maintain the target MAP decreased. The MAP value in each group was not significantly different during the whole experiment period. The values of the wet/dry weights and MIP-2 were significantly lower in the FFP:RBC = 1:1 group than the other groups (P < .05). All parameters detected above were predominantly lower in the FFP:RBC = 1:1 group than the FFP:RBC = 1:2 group and the LR:RBC = 1:1 group (P < .05). In addition, all parameter values were lower in the FFP:RBC = 1:1 group than in the FFP:RBC = 2:1 group, but only the wet/dry weight, myeloperoxidase, and MIP-2 values were significantly different (P < .05). CONCLUSIONS: Resuscitation with a 1:1 ratio of FFP to RBC results in decreased lung inflammation. Compared with LR, FFP could further mitigate lung inflammatory injury.
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Lesão Pulmonar/prevenção & controle , Plasma , Ressuscitação/métodos , Choque Hemorrágico/terapia , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Soluções Isotônicas , Lesão Pulmonar/metabolismo , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Lactato de Ringer , Choque Hemorrágico/metabolismoRESUMO
Endothelial activation elicited by inflammatory agents is regarded as a key event in the pathogenesis of several vascular inflammatory diseases. In the present study, the inhibitory effects and underlying mechanism of C-type natriuretic peptide (CNP) on LPS-induced endothelial activation were examined in human umbilical vein endothelial cells (HUVECs). The effect of CNP on adhesion molecule expression was assessed using quantitative real-time RT-PCR and western blotting analyses. The nuclear factor-κB (NF-κB), MAPK, and PI3K/Akt signaling pathways in LPS-stimulated HUVECs were investigated using western blotting analyses, and the production of intracellular reactive oxygen species (ROS) was measured using a fluorescence method. Pretreatment with CNP inhibited LPS-induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin in a concentration-dependent manner. CNP suppressed the phosphorylation of p65 and NF-κB activation in LPS-stimulated cells. Moreover, CNP reduced ERK1/2 and p38 phosphorylation induced by LPS but not JNK. Furthermore, CNP induced Akt phosphorylation and activation of hemeoxygenase-1 (HO-1) expression. CNP significantly inhibited the production of intracellular ROS. These results suggest that CNP effectively attenuated LPS-induced endothelial activation by inhibiting the NF-κB and p38 signaling pathways, eliminating LPS-induced intracellular ROS production, and activating the PI3K/Akt/HO-1 pathway in HUVECs; thereby, demonstrating that CNP may be a potential therapeutic target for the treatment of sepsis and inflammatory vascular diseases.
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Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipopolissacarídeos/metabolismo , Peptídeo Natriurético Tipo C/metabolismo , Transdução de Sinais , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised tumors, and may be a useful animal model for the evaluation of various therapeutic approaches for gliosarcomas. In this study, the 9L/Wistar rat glioma model was produced by intracerebral implantation of 9L(LUC) glioma cells syngenic to Fischer 344 (F344) rats. Bioluminescence imaging showed that tumors progressively grew from day 7 to day 21 in 9L(LUC)/F344 rats, and tumor regression was found in some 9L(LUC)/Wistar rats. Hematoxylin-eosin staining verified that intracranial tumors were gliomas. Immunohistochemistry results demonstrated that no CD4- and CD8-positive cells were found in the syngeneic 9L(LUC)/F344 model. However, many infiltrating CD4- and CD8-positive cells were observed within the tumors of the 9L(LUC)/Wistar model. Our data suggests that compared with 9L/F344 rats, 9L glioma Wistar rats may not be suitable for evaluating brain glioma immunotherapies, even though the model induced an immune response and exhibited tumor regression.
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This study was purpose to investigate the effects of CD147 on the invasiveness of leukemia cells U937. The experiments were divided into 4 groups: control group, LPS group, CD147mAb group and LPS+CD147 mAb group. Cells were treated by lipopolysaccharide (LPS) or anti-CD147 monoclonal antibody, and the expression of CD147 and MMP-2, -9, the invasive potential of the cells in vitro and ex vivo, as well as the invasion of the implanted tumors in SCID mice were analysed by RT-PCR, FCM, gel zymography and invasion test in vitro respectively. The results showed that the expression of CD147 was elevated by the induction of LPS, and the enhanced expression of CD147 on U937 cells increased the production and secretion of MMP-2 and MMP-9 as measured by reverse transcription-PCR and gel zymography. An increased number of LPS-induced cells invading through a reconstituted basement membrane were observed by invasion assays. These responses were down-regulated after blocking CD147 with anti-CD147 antibody. At 30 days after intravenous injection of LPS pretreated U937 cells to SCID mice human U937 cells were found in the bone marrow and lung of the mice, indicating the invasion of the tumor cells. And overexpressions of CD147, MMP-2 and MMP-9 were found in the lung tissue of the mice injected with LPS-treated but not anti-CD147 antibody treated tumor cells. It is concluded that overexpression of CD147 on U937 cells may increase the secretion and activation of MMP-2 and MMP-9 and thus promote the invasiveness of the tumor cells.