Medison.Sang Bong Ahn has received grants from Hanwha, Samjin, Ildong, and Hanmi.Dae Won Jun has served as an advisory committee member of Sysmax, J2H, and Future medicine. He is a speaker for Gilead Sciences,
Over the past decade, mesoporous silica nanoparticles (MSNs) smaller than 200 nm with a high colloidal stability have been extensively studied for systemic drug delivery. Although small molecule delivery via MSNs has been successful, the encapsulation of large therapeutic biomolecules, such as proteins or DNA, is limited due to small pore size of the conventional MSNs obtained by soft-templating. Here, we report the synthesis of mesoporous silica nanoparticles with extra-large pores (XL-MSNs) and their application to in vivo cytokine delivery for macrophage polarization. Uniform, size-controllable XL-MSNs with 30 nm extra-large pores were synthesized using organic additives and inorganic seed nanoparticles. XL-MSNs showed significantly higher loadings for the model proteins with different molecular weights compared to conventional small pore MSNs. XL-MSNs were used to deliver IL-4, which is an M2-polarizing cytokine and very quickly degraded in vivo, to macrophages and polarize them to anti-inflammatory M2 macrophages in vivo. XL-MSNs induced a low level of reactive oxygen species (ROS) production and no pro-inflammatory cytokines in bone marrow-derived macrophages (BMDMs) and in mice injected intravenously with XL-MSNs. We found that the injected XL-MSNs were targeted to phagocytic myeloid cells, such as neutrophils, monocytes, macrophages, and dendritic cells. Finally, we demonstrated that the injection of IL-4-loaded XL-MSNs successfully triggered M2 macrophage polarization in vivo, suggesting the clinical potential of XL-MSNs for modulating immune systems via targeted delivery of various cytokines.
Antiplatelet therapy reduces the risk of HCC in chronic hepatitis B patients whose hepatitis B virus is effectively suppressed. However, antiplatelet therapy containing clopidogrel may increase the risk of bleeding. (Hepatology 2017;66:1556-1569).
This new model using protein induced by vitamin K absence-II and alpha-fetoprotein provides refined prognostication. Among beyond-MC HCC patients, those with a MoRAL score ≤314.8 and without extrahepatic metastasis might be potential candidates for LDLT.
Fluid combined with forced-air warming is effective in decreasing the incidence of perioperative hypothermia and improving maternal thermal comfort. However, despite multimodal AW, the majority of women became hypothermic, and shivering was not prevented. The findings suggest that combined AW for cesarean delivery with spinal anesthesia is difficult, and only modest benefit should be expected.
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