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      • Human IL-32 expression protects mice against a hypervirulent strain of <i>Mycobacterium tuberculosis</i>

        Bai, Xiyuan,Shang, Shaobin,Henao-Tamayo, Marcela,Basaraba, Randall J.,Ovrutsky, Alida R.,Matsuda, Jennifer L.,Takeda, Katsuyuki,Chan, Mallory M.,Dakhama, Azzeddine,Kinney, William H.,Trostel, Jessica National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.16

        <P><B>Significance</B></P><P>Interleukin-32 (IL-32) is induced by IL-1β, Toll-like receptor agonists, and nucleotide oligomerization domain as well as by <I>Mycobacterium tuberculosis</I> (<I>MTB</I>). Expression of human IL-32γ in the lungs of mice reduced the burden of <I>MTB</I> in both the lungs but also in the spleen and was associated with increased survival. Mechanistically, increased numbers of host-protective innate and adaptive immune cells were present in the IL-32 transgenic mice. Alveolar macrophages from the transgenic mice were also better able to control <I>MTB</I> infection and had increased colocalization of <I>MTB</I> with lysosomes. IL-32 expression was increased in the surgically resected lungs of tuberculosis patients, particularly in macrophages, airway epithelial cells, B cells, and T cells. Thus, IL-32 enhances host immunity against <I>MTB</I>.</P><P>Silencing of interleukin-32 (IL-32) in a differentiated human promonocytic cell line impairs killing of <I>Mycobacterium tuberculosis</I> (<I>MTB</I>) but the role of IL-32 in vivo against <I>MTB</I> remains unknown. To study the effects of IL-32 in vivo, a transgenic mouse was generated in which the human <I>IL-32γ</I> gene is expressed using the surfactant protein C promoter (SPC-IL-32γTg). Wild-type and SPC-IL-32γTg mice were infected with a low-dose aerosol of a hypervirulent strain of <I>MTB</I> (W-Beijing HN878). At 30 and 60 d after infection, the transgenic mice had 66% and 85% fewer <I>MTB</I> in the lungs and 49% and 68% fewer <I>MTB</I> in the spleens, respectively; the transgenic mice also exhibited greater survival. Increased numbers of host-protective innate and adaptive immune cells were present in SPC-IL-32γTg mice, including tumor necrosis factor-alpha (TNFα) positive lung macrophages and dendritic cells, and IFN-gamma (IFNγ) and TNFα positive CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T cells in the lungs and mediastinal lymph nodes. Alveolar macrophages from transgenic mice infected with <I>MTB</I> ex vivo had reduced bacterial burden and increased colocalization of green fluorescent protein-labeled <I>MTB</I> with lysosomes. Furthermore, mouse macrophages made to express IL-32γ but not the splice variant IL-32β were better able to limit <I>MTB</I> growth than macrophages capable of producing both. The lungs of patients with tuberculosis showed increased IL-32 expression, particularly in macrophages of granulomas and airway epithelial cells but also B cells and T cells. We conclude that IL-32γ enhances host immunity to <I>MTB</I>.</P>

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        Electrochemical Study of Three Stainless Steel Alloys and Titanium Metal in Cola Soft Drinks

        Peralta-Lopez, D.,Sotelo-Mazon, O.,Henao, J.,Porcayo-Calderon, J.,Valdez, S.,Salinas-Solano, G.,Martinez-Gomez, L. The Korean Electrochemical Society 2017 Journal of electrochemical science and technology Vol.8 No.4

        Stainless steels and titanium alloys are widely used in the medical industry as replacement materials. These materials may be affected by the conditions and type of environment. In the same manner, soft drinks are widely consumed products. It is of interest for dental industry to know the behavior of medical-grade alloys when these are in contact with soft drinks, since any excessive ion release can suppose a risk for human health. In the present study, the electrochemical behavior of three stainless steel alloys and pure titanium was analyzed using three types of cola soft drinks as electrolyte. The objective of this study was to evaluate the response of these metallic materials in each type of solution (cola standard, light and zero). Different electrochemical techniques were used for the evaluation of the alloys, namely potentiodynamic polarization, linear polarization, and open-circuit potential measurements. The corrosion resistance of the stainless-steel alloys and titanium in the cola soft drinks was provided by the formation of a stable passive film formed by metal oxides. Scanning electron microscopy was used as a complementary technique to reveal corrosion phenomena at the surface of the materials evaluated.

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        Preemptive Analgesia with Acupuncture Monitored by c-Fos Expression in Rats

        André T.A. Gonçalves de Freitas,Lino Lemonica,Julio De Faveri,Sergio Pereira,Maria D. Bedoya Henao 사단법인약침학회 2016 Journal of Acupuncture & Meridian Studies Vol.9 No.1

        Pain behavior and awareness are characterized by heightened alertness and anxiety, which begin to disappear as soon as the curative process starts. The present study aimed to quantify c-fos expression in rat spinal cords and brains after a surgical stimulus and with preoperative or postoperative acupuncture. Animals were randomly divided into preoperative and postoperative groups and were then further divided into control, manual acupuncture (MA), or electroacupuncture (EA) groups. Expression of c-fos was quantified using immunohistochemistry. The collected data were analyzed using the t test at a 5% probability level. Presurgery and postsurgery spinal cord c-fos expressions were similar in all of the treatment groups. In the control rats, c-fos expression was higher before surgery than after surgery, contradicting the expected outcome of acupuncture and preemptive analgesia. After treatment, the expression of c-fos in the brains of the rats in the MA and the EA groups was reduced compared with that of the rats in the control group. These findings suggest that acupuncture used as preemptive analgesia in rats is a useful model for studying its application in human treatment.

      • A Network of Substrates of the E3 Ubiquitin Ligases MDM2 and HUWE1 Control Apoptosis Independently of p53

        Kurokawa, Manabu,Kim, Jiyeon,Geradts, Joseph,Matsuura, Kenkyo,Liu, Liu,Ran, Xu,Xia, Wenle,Ribar, Thomas J.,Henao, Ricardo,Dewhirst, Mark W.,Kim, Wun-Jae,Lucas, Joseph E.,Wang, Shaomeng,Spector, Neil L AAAS 2013 Science signaling Vol.6 No.274

        <P><B>Breaking Down to Build Resistance</B></P><P>Chemotherapeutic resistance often arises because of the rewiring of signaling pathways in cancer cells. Kurokawa <I>et al.</I> found that the ubiquitin E3 ligase MDM2 triggered the breakdown of another ubiquitin E3 ligase, HUWE1. In breast cancer cells that died when exposed to the HER2 (human epidermal growth factor receptor 2) EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor lapatinib, MDM2 was degraded, which enabled HUWE1 to trigger the degradation of a prosurvival protein and promote assembly and activation of a protein complex required for the execution of cell death. However, MDM2 degradation did not occur in lapatinib-resistant breast cancer cells, and thus, the abundance of HUWE1 was decreased, promoting cell survival. In a mouse xenograft model, an inhibitor of MDM2 reduced the growth of tumors generated from lapatinib-resistant breast cancer cells. Thus, MDM2 could be targeted to circumvent resistance to lapatinib in breast cancers.</P>

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