Our results support that H5N6 virus could potentially be a major public health threat, and suggest it is possible that the earlier acquisition of cellular immunity and lower concentrations of cytokines/chemokines contributed to survival in our patient. Analysis of more patient samples will be needed to draw concrete conclusions.

No abstract

In this work, a novel type of pH-sensitive multifunctional envelope-type mesoporous silica nanocontainers (SBDAPF) was constructed for targeted drug delivery to cancer cells. Poly(N-succinimidyl acrylate) was coated on the mesoporous silica nanoparticles surface via an acid-labile acetal linker to obtain the SBA particles for pH-triggered drug release. A model drug doxorubicin (DOX)-loaded SBA system (SBDA) showed low premature drug release at neutral pH and effective stimuli-responsive release under the acidic conditions. To provide the colloidal stability and avoid nonspecific uptake of normal or healthy cells, the SBDA nanocontainers were modified with a poly(ethylene glycol) (PEG) polymer to form a protection layer. Furthermore, folic acid was introduced as a targeting component and anchored on the PEG outer layer to achieve the cancer-targeting ability. In vitro study demonstrated that SBDAPF could selectively adhere to the surface of cancer cells through the specific binding with folate receptor and be internalized into cells, subsequently releasing the entrapped DOX with high efficiency in slightly acidic intracellular microenvironment to finally kill cancer cells. Such a versatile drug delivery system as SBDAPF should have a potential application in cancer therapy.

Angiogenesis in atherosclerotic plaque promotes plaque growth, causes plaque hemorrhage, and violates plaque stability. LINC00657 is a long noncoding RNA highly conserved and abundantly expressed in vascular endothelial cells. The present study was designed to investigate the effects and mechanisms of LINC00675 on low concentrations of oxidized low-density lipoprotein (oxLDL)-induced angiogenesis. Cell proliferation, transwell, wound healing, and tube formation assays were conducted to detect the effects of low concentrations of oxLDL on angiogenesis; the results discovered that oxLDL promoted cell proliferation, migration, and tube formation. oxLDL also upregulated LINC00657 expression. Inhibition of LINC00657 by siRNA significantly suppressed oxLDL-induced endothelial cell proliferation, migration, and tube formation. Bioinformatic assay indicated six binding sites in the LINC00657 sequence to miR-590-3p. The upregulation of LINC00657 was related to the downregulation of miR-590-3p in oxLDL-treated endothelial cells; while downregulation of LINC00657 resulted in upregulation of miR-590-3p. The antiangiogenesis effects of si-LINC00657 were partly abrogated by miR-590-3p inhibitor. Further dual-luciferase assay found miR-590-3p inhibited the expression of hypoxia-inducible factor 1 (HIF-1) by binding to the position of 689-696 in HIF-1 3'-untranslated region directly. MiR-590-3p also inhibited the oxLDL-induced upregulation of HIF-1, vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). These results suggested that in oxLDL-treated endothelial cells, LINC00657 acted as a miR-590-3p sponge to attenuate the suppression of miR-590-3p on HIF-1, and to promote angiogenesis through VEGF, MMP-2, and MMP-9. The present study provided new insight into the roles of LINC00657 and miR-590-3p in preventing oxLDL-induced angiogenesis and may provide a novel strategy for atherosclerosis treatment.