Anti-CD137 mAb Deletes Both Donor CD4+ and CD8+ T Cells in Acute Graft-versus-host Disease

We previously demonstrated that in vivo engagement of CD137, a member of TNF receptor superfamily, can delete allorective CD4+ T cells through the induction of activation-induced cell death (AICD) in chronic graft-versus-host disease (cGVHD) and subsequently reverse established cGVHD. In this study, we further showed that agonistic anti-CD137 mAb was highly effective in triggering AICD of donor CD8+ T cells as well as donor CD4+ T cells in the C57BL/6→unirradiated (C57BL/6 × DBA/2)F1 acute GVHD model. Our results suggest that strong allostimulation should facilitate AICD of both alloreactive CD4+ and CD8+ T cells induced by CD137 stimulation. Therefore, depletion of pathogenic T cells using agonistic anti-CD137 mAb combined with potent TCR stimulation may be used to block autoimmune or inflammatory diseases mediated by T cells

Serum Vitamin E is Associated with Osteoarthritis among Korean Older Adults

Objectives: We aimed to examine the cross-sectional association between serum vitamin E level and osteoarthritis in Korean older adults. Methods: Data from the Korea National Health and Nutrition Examination Survey 2016 – 2018 were used. Overall, 978 participants aged ≥ 65 years were included in the study. Demographic, lifestyle, and health data were obtained through interviews or self-reported questionnaires. Patients with osteoarthritis were defined if they had responded “yes” to any of these three questions related to diagnosis, current condition, and treatment. Multivariate logistic regression analysis was performed to assess the association between serum vitamin E level and osteoarthritis. Results: After multivariate adjustment, a higher level of vitamin E was found to be associated with a higher prevalence of osteoarthritis (Odds ratio: 2.27, 95 % Confidence Interval: 1.19 – 4.34, p for trend = 0.037). Conclusion: A higher level of serum vitamin E was associated with increased osteoarthritis prevalence in older Koreans. Further prospective or clinical studies are needed to verify the causality

Drug delivery by a self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells

A DNA tetrahedron is employed for efficient delivery of doxorubicin into drug-resistant breast cancer cells. The drug delivered with the DNA nanoconstruct is considerably cytotoxic, whereas free doxorubicin is virtually non-cytotoxic for the drug-resistant cells. Thus, the DNA tetrahedron, made of the inherently natural and biocompatible material, can be a good candidate for the drug carrier to overcome MDR in cancer cells.close11

Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

Background: Titanium dioxide (TiO2) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25-70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25-70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials.This work was supported by the Korea Ministry of Environment and The Eco-Technopia 21 Project (091-091-081)

Identification of gp96 as a Novel Target for Treatment of Autoimmune Disease in Mice

Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Chronic expression of heat shock protein gp96 on cell surfaces induces significant DC activations and systemic lupus erythematosus (SLE)-like phenotypes in mice. However, its potential as a therapeutic target against SLE remains to be evaluated. In this work, we conducted chemical approach to determine whether SLE-like phenotypes can be compromised by controlling surface translocation of gp96. From screening of chemical library, we identified a compound that binds and suppresses surface presentation of gp96 by facilitating its oligomerization and retrograde transport to endoplasmic reticulum. In vivo administration of this compound reduced maturation of DCs, populations of antigen presenting cells, and activated B and T cells. The chemical treatment also alleviated the SLE-associated symptoms such as glomerulonephritis, proteinuria, and accumulation of anti-nuclear and –DNA antibodies in the SLE model mice resulting from chronic surface exposure of gp96. These results suggest that surface translocation of gp96 can be chemically controlled and gp96 as a potential therapeutic target to treat autoimmune disease like SLE

Huge carotid body paraganglioma

A 33-year-old woman was admitted to our hospital with a slow-growing mass in the left side of her neck. The mass was found to be a huge (73 × 56 × 54 mm) carotid body paraganglioma. Another 21 mm-size tumor was incidentally detected at the right carotid bifurcation. She had hoarseness and Horner's syndrome of her left side. Both tumors were surgically removed. There were no cerebrovascular complications but some neurologic complications occurred when the left tumor was removed