Uptake of biodegradable poly(γ-glutamic acid) nanoparticles and antigen presentation by dendritic cells in vivo

AbstractPoly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) carrying antigens have been shown to induce potent antigen-specific immune responses. However, in vivo delivery of γ-PGA NPs to dendritic cells (DCs), a key regulator of immune responses, still remains unclear. In this study, γ-PGA NPs were examined for their uptake by DCs and subsequent migration from the skin to the regional lymph nodes (LNs) in mice. After subcutaneous injection of fluorescein 5-isothiocyanate (FITC)-labeled NPs or FITC-ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs), DCs migrated from the skin to the LNs and maturated, resulting in the upregulation of the costimulatory molecules CD80 and CD86 and the chemokine receptor CCR7. However, the migrated DCs were not detected in the spleen. FITC-OVA-NPs were found to be taken up by skin-derived CD103+ DCs, and the processed antigen peptides were cross-presented by the major histocompatibility complex (MHC) class I molecule of DCs. Furthermore, significant activation of antigen-specific CD8+ T cells was observed in mice immunized with OVA-carrying NPs (OVA-NPs) but not with OVA alone or OVA with an aluminum adjuvant. The antigen-specific CD8+ T cells were induced within 7 days after immunization with OVA-NPs. Thus, γ-PGA NPs carrying various antigens may have great potential as an antigen-delivery system and vaccine adjuvant in vivo

How Are Tier 2 Metropolises Affected by Housing Asset Value Deflation in the Depopulation Era? A Comparison between the Tokyo and Kansai Metropolitan Areas

International audienceThis study analyzes the differences and similarities between Tier 1 (Tokyo) and Tier 2 (Kansai) metropolitan areas due to shrinking city problems. Both metropolitan areas will see a dramatic decrease in the housing asset value (HAV). Kansai is declining at a faster pace than Tokyo: it is projected that HAVs will register a further decrease of around 38% by 2045, and the decline will be quantitatively more important in the northern suburbs of Osaka. These results raised the question of whether Kansai would be more impoverished by HAV deflation. By focusing on the income multiplier of HAV per household, we find that Tokyo has a higher income multiplier of around 4 (against 2 for Osaka), thus causing much greater HAV deflation per household in Tokyo. Greater HAV deflation per household entails more severe problems for elderly households that need to finance their retirement. Considering our findings, despite earlier and faster trends of HAV deflation in the Tier 2 metropolitan area, the Tier 1 metropolitan area could face big socioeconomic challenges in the future. We conclude that HAV deflation leads to problems of different nature depending on metropolitan rank, rather than just knowing which one is losing more through HAV deflation

Effects of housing asset deflation on shrinking cities: A case of the Tokyo metropolitan area

International audienc

Serum levels of apoptosis inhibitor of macrophage are associated with hepatic fibrosis in patients with chronic hepatitis C

Background: Apoptosis inhibitor of macrophage (AIM) and adipocytokines are involved in the metabolic syndrome, which has been putatively associated with the progression of chronic hepatitis C (CHC). However, the association between these cytokines and CHC is not fully elucidated. The aim of this study is to test whether serum levels of AIM and adipocytokines are associated with histological features, homeostasis model assessment-insulin resistance index (HOMA-IR), or whole body insulin sensitivity index (WBISI) in CHC patients.Methods: Serum samples were obtained from 77 patients with biopsy-proven CHC. In 39 patients without overt diabetes mellitus, a 75 g oral glucose tolerance test (OGTT) was performed and HOMA-IR and WBISI were calculated.Results: A serum AIM level of ?1.2 μg/ml was independently associated with advanced hepatic fibrosis (F2 or F3) (odds ratio [OR], 5.612; 95% confidence interval [CI], 1.103-28.563; P = 0.038) based on a multivariate analysis, but there was no significant association between AIM and hepatic steatosis or inflammation. Furthermore, a serum leptin level of ?8.6 ng/ml was independently associated with the presence of hepatic steatosis (?5%) (OR, 6.195; 95% CI, 1.409-27.240; P = 0.016), but not hepatic fibrosis or inflammation. No relationship was observed between levels of adiponectin or resistin and hepatic histological parameters based on a multivariate analysis. Although serum levels of leptin, resistin, and adiponectin were significantly correlated with HOMA-IR and WBISI, there was no significant relationship between serum AIM levels and HOMA-IR or WBISI, respectively.Conclusion: High serum levels of AIM in CHC patients are potentially related to advanced hepatic fibrosis. AIM and adipocytokines are possibly associated with pathological changes via a different mechanism