Universal Strategy of Efficient Intracellular Macromolecule Directional Delivery Using Photothermal Pump Patch.

The development of a highly efficient, nondestructive, and in vitro/vivo-applicable universal delivery strategy of therapeutic macromolecules into desired cells and tissues is very challenging. Photothermal methods have advantages in intracellular delivery, particularly in in vivo manipulation. However, the inability of directional transmission of exogenous molecules limits their delivery efficiency. Here, a photothermal pump (PTP) patch with numerous "exogenous molecular reservoirs" is reported. Under a laser, the cell membrane ruptures, while "exogenous molecular reservoirs" shrink, resulting in a directional exogenous molecule delivery into cells for a high-efficient intracellular delivery. The PTP patches are considered a universal structure for a highly efficient, nondestructive, and in-vitro/vivo-applicable intracellular macromolecule delivery. Under in vivo transdermal intracellular delivery conditions, the target genes are efficiently and noninvasively delivered into epidermal and dermal cells through the PTP patch and exosomes produced by the epidermal cells, respectively. The PTP patch provides a new strategy for a high-efficiency, nondestructive, and in-vitro/vivo-applicable macromolecule delivery.

Bone Marrow-Derived Mesenchymal Stem Cells Transplantation Attenuates Renal Fibrosis Following Acute Kidney Injury in Rats by Diminishing Pericyte-Myofibroblast Transition and Extracellular Matrix Augment.

BACKGROUND: Renal fibrosis is a common chronic outcome of acute kidney injury (AKI). Pericyte-myofibroblasts transition and production of abundant extracellular matrix are the important pathologic basis. This study investigated the effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on the AKI kidney fibrosis and the possible mechanisms. METHODS: By constructing the animal and cell model of AKI pericyte injury, the therapeutic effect of BMSCs on pericyte-myofibroblasts transition was detected. The production and accumulation of extracellular matrix, including collagen I, collagen III, and fibronectin were also tested. The mechanism was revealed by means of analysis of signal pathway. RESULTS: After AKI insult, many myofibroblasts emerged in the renal interstitium together with a large amount of extracellular matrix components. The BMSCs transplantation significantly decreased the number of myofibroblasts trans-differentiated from pericytes in the AKI model. The changes of vascular endothelial growth factor subtypes and Ang-I/AngII secreted by pericytes were also significantly reduced after BMSCs co-culture. At the same time, extracellular matrix components, including collagen I, collagen III, and fibronectin, decreased significantly. Transplantation treatment alleviated the fibrosis score. The transforming growth factor ß (TGF-ß) concentration decreased as well as the levels of Smad2/3 and p-Smad2/3 with the presence of BMSCs therapy. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells transplantation diminished pericyte-myofibroblast transition and extracellular matrix augment after AKI by regulating the TGF-ß/Smad2/3 signaling pathway. It may be used as a novel therapeutic method for retarding renal fibrosis, which is worthy of further study.

Quick and improved immune responses to inactivated H9N2 avian influenza vaccine by purified active fraction of Albizia julibrissin saponins.

BACKGROUND: H9N2 Low pathogenic avian influenza virus (LPAIV) raises public health concerns and its eradication in poultry becomes even more important in preventing influenza. AJSAF is a purified active saponin fraction from the stem bark of Albizzia julibrissin. In this study, AJSAF was evaluated for the adjuvant potentials on immune responses to inactivated H9N2 avian influenza virus vaccine (IH9V) in mice and chicken in comparison with commercially oil-adjuvant. RESULTS: AJSAF significantly induced faster and higher H9 subtype avian influenza virus antigen (H9-Ag)-specific IgG, IgG1, IgG2a and IgG2b antibody titers in mice and haemagglutination inhibition (HI) and IgY antibody levels in chicken immunized with IH9V. AJSAF also markedly promoted Con A-, LPS- and H9-Ag-stimulated splenocyte proliferation and natural killer cell activity. Furthermore, AJSAF significantly induced the production of both Th1 (IL-2 and IFN-γ) and Th2 (IL-10) cytokines, and up-regulated the mRNA expression levels of Th1 and Th2 cytokines and transcription factors in splenocytes from the IH9V-immunized mice. Although oil-formulated inactivated H9N2 avian influenza vaccine (CH9V) also elicited higher H9-Ag-specific IgG and IgG1 in mice and HI antibody titer in chicken, this robust humoral response was later produced. Moreover, serum IgG2a and IgG2b antibody titers in CH9V-immunized mice were significantly lower than those of IH9V alone group. CONCLUSIONS: AJSAF could improve antigen-specific humoral and cellular immune responses, and simultaneously trigger a Th1/Th2 response to IH9V. AJSAF might be a safe and efficacious adjuvant candidate for H9N2 avian influenza vaccine.