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ABSTRACT: NiFe2O4 nanorods have been successfully synthesized via thermal treatment of the rod-like precursor fabricated by Ni-doped α-FeOOH,
which was enwrapped by the complex of citric acid and Ni2+. The morphology evolution during the calcination of the precursor nanorods was investigated with transmission electron microscopy
(TEM), and the phase and the magnetic properties of samples were analyzed through X-ray diffraction (XRD) and vibrating sample
magnetometer (VSM). The results indicated that the diameter of the NiFe2O4 nanorods obtained ranged between 30 and 50 nm, and the length ranged between 2 and 3 μm. As the calcination temperature was
up to 600°C, the coercivity, saturation magnetization, and remanent magnetization of the samples were 36.1 kA·m−1, 27.2 A·m2·kg−1, and 5.3 A·m2·kg−1, respectively. The NiFe2O4 nanorods prepared have higher shape anisotropy and superior magnetic properties than those with irregular shapes.
Keywordsinorganic compounds-nickel ferrite-nanorods-electron microscopy-magnetic properties
Rare Metals 04/2012; 29(4):385-389. · 0.59 Impact Factor
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ABSTRACT: Tuberculosis (TB) remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG), has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease. Here, we constructed a recombinant Mycobacterium smegmatis (rMS) strain expressing a fusion protein of heparin-binding hemagglutinin (HBHA) and human interleukin 12 (hIL-12). Immune responses induced by the rMS in mice and protection against Mycobacterium tuberculosis (MTB) were investigated. Administration of this novel rMS enhanced Th1-type cellular responses (IFN-γ and IL-2) in mice and reduced bacterial burden in lungs as well as that achieved by BCG vaccination. Meanwhile, the bacteria load in M. tuberculosis infected mice treated with the rMS vaccine also was significantly reduced. In conclusion, the rMS strain expressing the HBHA and human IL-12 fusion protein enhanced immunogencity by improving the Th1-type response against TB, and the protective effect was equivalent to that of the conventional BCG vaccine in mice. Furthermore, it could decrease bacterial load and alleviate histopathological damage in lungs of M. tuberculosis infected mice.
PLoS ONE 01/2012; 7(2):e31908. · 4.09 Impact Factor
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ABSTRACT: The secreted Mycobacterium tuberculosis (MTB) proteins, Ag85B and Hsp16.3, have been the focus of intensive research in recent years. These proteins have high sensitivity in bacterium-negative tuberculosis (TB) patients, and are valuable for the rapid diagnosis of bacterium-negative TB. Fusion proteins including multiple antigens such as Ag85B and Hsp16.3 provide improved sensitivity and specificity for serological diagnosis of active TB compared with a single antigen. Many studies have shown that the production of MAbs recognizing a specific repertoire of M. tuberculosis antigens and the tests based on monoclonal antibodies have been found to be valuable in positive detection of TB, particularly for smear-positive pulmonary TB. A number of MAbs are currently used for serodiagnosis of TB. Therefore, an Ag85B-Hsp16.3 fusion protein was expressed and purified using an E. coli system in this study. Three Ag85B-Hsp16.3 fusion protein-specific MAbs were generated by routine murine hybridoma techniques. The titer, specificity, and relative affinity of all three MAbs were determined by ELISA and the serological responses were analyzed. The levels of antigens in a proportion of TB patients were shown to be significantly higher than those in healthy controls. The sensitivity and specificity of the currently available detection systems is likely to be improved by the employment of a combination of these MAbs with others that are already in use.
Hybridoma (2005) 10/2011; 30(5):427-32. · 0.42 Impact Factor
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ABSTRACT: The mechanisms of latency and the causes of reactivation of Mycobacterium tuberculosis remain poorly understood; an important reason for this gap in knowledge is the absence of a standardized animal model of latent tuberculosis infection (LTBI). A complete LTBI model should incorporate 2 aspects of LTBI: a persistent infection model with a low bacterial load and a latent infection model that is modified from the Cornell model. Many parameters must be carefully considered to establish an LTBI model, including the inoculating dose, the route of infection, the time interval between infection and the initiation of antibiotic therapy, and the genetic background of the host animal. The responsiveness of this mouse model of LTBI can be assessed through the integrated use of indices, including Karnofsky performance status, bacterial load in spleen and lungs, induced levels of interferon-gamma and tumour necrosis factor-alpha, expression of interleukin (IL)-10 and IL-4 in tissues, specific antigen load in organs, time required for hormone-induced TB relapse, expression level of dormancy genes, and CD4 T-cell count.
Scandinavian Journal of Infectious Diseases 09/2011; 43(11-12):848-56. · 1.72 Impact Factor
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ABSTRACT: Autophagy plays specific roles in host innate and adaptive immune responses to numerous intracellular pathogens, including Mycobacterium tuberculosis. The ESAT-6 and CFP-10 proteins are secreted by M. tuberculosis and play important roles in pathogenesis. We hypothesized that these two proteins may affect the autophagy function of host macrophages during infection with M. tuberculosis, thereby shaping the immune reaction toward the pathogen. Interestingly, we found that rapamycin-induced autophagy of macrophages infected with M. tuberculosis H37Rv enhanced localization of mycobacteria with autophagosomes and lysosomes. Ectopic expression of the ESAT-6/CFP-10 fusion in macrophages dramatically inhibited autophagosome formation, and M. tuberculosis survival inside infected macrophages was significantly affected as well. Further, M. tuberculosis viability was increased by the fusion protein. Expression levels of autophagy-related genes (ATG), especially atg8, also decreased (p<0.05). These results suggested that ESAT-6 and CFP-10 proteins play significant roles in autophagy formation in M. tuberculosis infection and that autophagosome formation is regulated through the expression of ATG.
DNA and cell biology 07/2011; 31(2):171-9. · 2.28 Impact Factor
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ABSTRACT: Current tuberculosis control measures are focused on the prompt detection and treatment of active tuberculosis. Despite the measured success of this strategy, tuberculosis continues to be a public health issue of major significance around the world. This unwanted situation suggests the need to expand our control efforts by exploring specific markers for the disease. Insulin resistance is one such marker. Although insulin resistance has been implicated in various diseases, thus far, no attempt has been made to analyze what has proved to be a direct relationship between insulin resistance and Mycobacterium tuberculosis susceptibility. Several studies have shown the role of insulin not only in cellular metabolism but also, more importantly, in phagocytosis of M. tuberculosis. Therefore, we hypothesize that insulin resistance can be considered a potential risk factor for active M. tuberculosis infection.
Medical Hypotheses 04/2011; 77(1):66-8. · 1.39 Impact Factor
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ABSTRACT: Mucin-1 (MUC1) is a breast tumor-associated antigen. However, clinical trials with MUC1 showed that, with respect to its expression levels, MUC1 is a relatively poor immunogen in human beings. Evidence showed that MUC1-specific immunodominant B and T cell epitopes are derived from the variable-number tandem repeat (VNTR) region. Therefore, immunotherapy that targets multiple VNTRs may induce anti-MUC1 immune responses. GM-CSF has been shown to increase the percentage and activity of antigen-presenting cells. In this study, we constructed two recombinant Bacillus Calmette-Guérin (BCG) vaccines that combine the expression of multiple tandem repeats of MUC1 and CSF. The effect of two novel breast cancer vaccines (rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF) on the growth of breast tumor on hu-PBL-SCID mice was evaluated.
We coupled VNTRs (4 and 8) of MUC1 with GM-CSF (MVNTR4-CSF and MVNTR8-CSF). The MVNTR4-CSF and MVNTR8-CSF were inserted into the pDE22 plasmid and transformed into competent BCG by electroporation. The effect of both BCG vaccines on the growth of breast tumor on hu-PBL-SCID mice was evaluated.
The growth of MUC1-positive breast tumors from hu-PBL-SCID mice immunized with two vaccines was significantly inhibited.
rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF vaccines may be good candidates for breast tumor immunotherapy.
Journal of Cancer Research and Clinical Oncology 09/2010; 136(9):1359-67. · 2.56 Impact Factor
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ABSTRACT: RpfB, one of the five resuscitation-promoting factors (Rpfs) produced by Mycobacterium tuberculosis (MTB), plays an important role in the resuscitation and growth of the dormant MTB. RpfB is likely the target antigen recognized by the host immune system. Studies have shown that Rpf genes exist in many bacteria and their encoded proteins all contain Rpf-like domain. It is likely that this domain has biological characteristics and immunogenicity similar to that of the complete Rpf protein. Therefore, RpfB domain protein from M. tuberculosis was selected for this study. Mice were subcutaneously immunized three times over 2-week intervals. Mice splenocytes were then isolated and fused with SP20 cells. Hybridoma colonies were screened for monoclonal antibody (MAb) against RpfB domain. ELISA was used to examine the titer, specificity, and relative affinity of the antibody. The ability of produced anti-RpfB monoclonal antibody to recognize other proteins in the Rpf family and to inhibit the growth of Mycobacterium tuberculosis and Micrococcus luteus was examined. Our results showed that three anti-RpfB MAbs were successfully generated. All three MAbs can recognize RpfB domain specifically and can effectively inhibit the promoting effect of RpfB domain on the growth of MTB H37Ra strain and M. luteus at 1:1000 dilution, indicating that anti-RpfB domain MAbs may inhibit the reactivation of dormant or latent MTB in vivo. Therefore, they may be able to prevent the recurrence of the occult infection. The production of anti-RpfB domain MAbs provides a powerful experimental tool to further study the biological and immunological characteristics of the RpfB domain and to evaluate the possibility of using RpfB domain as a candidate component for tuberculosis subunit vaccine.
Hybridoma (2005) 08/2010; 29(4):327-32. · 0.42 Impact Factor
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ABSTRACT: The challenge in breast cancer vaccine development is to find the best combination of antigen, adjuvant and delivery system to produce a strong and long-lasting immune response. Mucin 1 (MUC1) is a potential candidate target for breast cancer immunotherapy. Bacillus Calmette-Guerin (BCG) is used widely in human vaccines. Furthermore, it can potentially offer unique advantages for developing a safe and effective multi-vaccine vehicle. Due to these properties, the development of MUC1 based recombinant BCG (rBCG) vaccines for breast cancer immunotherapy has gained great momentum in recent years.
Our aim is to discuss the recent progress in MUC1-based breast cancer immunotherapy and to highlight the advantages of MUC1-based rBCG vaccines as the new breast cancer vaccines.
Several promising MUC1-based rBCG vaccines have been shown to induce MUC1-specific antitumor immune responses in pre-clinical studies. This review updates and evaluates this very important and rapidly developing field, and provides a critical perspective and information source for its potential clinical applications.
MUC1-based rBCG vaccines have been shown to elicit an effective anti-tumor immune response in vivo demonstrating its potential utility in breast cancer treatment.
Expert opinion on biological therapy 07/2010; 10(7):1037-48. · 3.22 Impact Factor
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ABSTRACT: Many approaches targeting MUC1 for breast tumor immunotherapy have been attempted. However, preclinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in human. B7 molecules that bind CD28 provide an antigen-nonspecific signal, which, along with an antigen-specific signal, is crucial for T-cell activation. In the present study, we constructed a novel Bacillus Calmette-Guérin-based breast cancer vaccine that coexpressed four VNTRs (variable-number tandem repeats) of MUC1 and CD80 (rBCG-MVNTR4-CD80). The aim of our study was to enhance anti-MUC1 tumor immunity by vaccination of hu-PBL-SCID mice with the recombinant BCG vaccine. The inhibition effect on tumors from the mice immunized with rBCG-MVNTR4-CD80 significantly increased, compared with rBCG-MVNTR4, BCG-pDE22, and phosphate-buffered saline immunized mice (p < 0.05, p < 0.05, p < 0.05). ELISpot assays showed that there was a significant increase in interferon-gamma production in the splenocytes from the mice immunized with rBCG-MVNTR4-CD80. In addition, CD4 and CD8-positive lymphocytes in tumors from rBCG-MVNTR4-CD80-immunized animals were detected. These data showed that rBCG-MVNTR4-CD80 immunization elicited tumor-specific immune response, which closely related with the B7 molecule (CD80), indicating that the vaccine may be a good candidate for MUC1-positive breast cancer immunotherapy.
Cancer Biotherapy & Radiopharmaceuticals 10/2009; 24(5):607-13. · 1.44 Impact Factor
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ABSTRACT: In this study, we constructed several novel breast cancer vaccines, Bacillus Calmette-Guérin (BCG)-MUC1 variable-number tandem repeats (VNTR) 1/4/8-CSF, that consist of BCG and express 1, 4, and 8 of the tandem repeats of MUC1 and human granulocyte-macrophage colony-stimulating factor (GM-CSF). The ability of the three recombinant BCG vaccines to inhibit breast cancer growth was observed in human (hu)-peripheral blood lymphocyte (PBL)-severe combined immunodeficient (SCID) mice. Prophylactic protective responses were successfully induced and the tumor incidence in mice immunized with recombinant BCG (rBCG)-MVNTR4-CSF (37.5%) or rBCG-MVNTR8-CSF (25%) was significantly decreased compared with control (100%) at 42 days after tumor implantation (P<0.05 vs. control group). We also found that CD4-positive and CD8-positive lymphocytes were detected only in tumors grown in rBCG-MVNTR4/8-CSF-immunized animals, and strong IFN-gamma responses were induced by immunization with rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF vaccines. This study suggests a potential role of coexpressed GM-CSF and tandem repeats of MUC1 in eliciting tumor-specific immune response. Our results indicate that rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF immunization preventively inhibited breast cancer growth in hu-PBL-SCID mice and the both rBCG vaccines may be good candidates for breast cancer immunotherapy.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2009; 18(5):416-23. · 2.21 Impact Factor
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ABSTRACT: In an attempt to improve immune responses and protective efficacy, we constructed two recombinant bacille Calmette-Guérin (rBCG) strains expressing an 85B antigen (Ag85B) and early secreted antigenic target-6 kDa antigen (ESAT6) of Mycobacterium tuberculosis (MTB) fusion protein. Both rBCG strains have the same protein insertion but in a different order (Ag85B-ESAT6 and ESAT6-Ag85B). The cultured supernatant of rBCG strains and the sera from the mice immunized with the fusion protein Ag85B-ESAT6 or ESAT6-Ag85B formed a band with a fraction size of 37 kDa, equalivalent to the sum of Ag85B and ESAT6. Six weeks after BALB/c mice were immunized with BCG or rBCG, spleen lymphocytes showed significant proliferation in response to culture filtrate protein of MTB. Compared with the BCG group, mice vaccinated with rBCG elicited a high level increase of immunoglobulin G antibodies to culture filtrate protein in the serum. The gamma-interferon levels in the lymphocyte culture medium supernatants increased remarkably in the rBCG1 group, significantly higher than that of the BCG immunized group (p<0.05). Four weeks after vaccination, mice were infected with M. tuberculosis H37Rv and a dramatic reduction in the numbers of MTB colony forming units in the spleens and lungs was observed in the two rBCG immunization groups. Although these rBCG strains were more immunogenic, their protective effect was comparable to the classical BCG strain, and there were no significant differences between two rBCG groups (p>0.05).
Acta Biochimica et Biophysica Sinica 04/2007; 39(4):290-6. · 1.38 Impact Factor
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ABSTRACT: In an attempt to improve immune responses and protective efficacy, we constructed two recombinant bacille Calmette-Guérin (rBCG) strains expressing an 85B antigen (Ag85B) and early secreted antigenic target-6 kDa antigen (ESAT6) of Mycobacterium tuberculosis (MTB) fusion protein. Both rBCG strains have the same protein insertion but in a different order (Ag85B-ESAT6 and ESAT6-Ag85B). The cultured supernatant of rBCG strains and the sera from the mice immunized with the fusion protein Ag85B- ESAT6 or ESAT6-Ag85B formed a band with a fraction size of 37 kDa, equalivalent to the sum of Ag85B and ESAT6. Six weeks after BALB/c mice were immunized with BCG or rBCG, spleen lymphocytes showed significant proliferation in response to culture filtrate protein of MTB. Compared with the BCG group, mice vaccinated with rBCG elicited a high level increase of immunoglobulin G antibodies to culture filtrate protein in the serum. The γ-interferon levels in the lymphocyte culture medium supernatants increased remarkably in the rBCG1 group, significantly higher than that of the BCG immunized group (P0.05).
Acta Biochimica Et Biophysica Sinica - ACTA BIOCHIM BIOPHYS SINICA. 01/2007; 39(4):290-296.
