A targeted hydrodynamic gold nanorod delivery system based on gigahertz acoustic streaming.

The hydrodynamic method mimics the in vivo environment of the mechanical effect on cell stimulation, which not only modulates cell physiology but also shows excellent intracellular delivery ability. Herein, a hydrodynamic intracellular delivery system based on the gigahertz acoustic streaming (AS) effect is proposed, which presents powerful targeted delivery capabilities with high efficiency and universality. Results indicate that the range of cells with AuNR introduction is related to that of AS, enabling a tunable delivery range due to the adjustability of the AS radius. Moreover, with the assistance of AS, the organelle localization delivery of AuNRs with different modifications is enhanced. AuNRs@RGD is inclined to accumulate in the nucleus, while AuNRs@BSA tend to enter the mitochondria and AuNRs@PEGnK tend to accumulate in the lysosome. Finally, the photothermal effect is proved based on the large quantities of AuNRs introduced via AS. The abundant introduction of AuNRs under the action of AS can achieve rapid cell heating with the irradiation of a 785 nm laser, which has great potential in shortening the treatment cycle of photothermal therapy (PTT). Thereby, an efficient hydrodynamic technology in AuNR introduction based on AS has been demonstrated. The outstanding location delivery and organelle targeting of this method provides a new idea for precise medical treatment.

Manipulation of single cells via a Stereo Acoustic Streaming Tunnel (SteAST).

At the single-cell level, cellular parameters, gene expression and cellular function are assayed on an individual but not population-average basis. Essential to observing and analyzing the heterogeneity and behavior of these cells/clusters is the ability to prepare and manipulate individuals. Here, we demonstrate a versatile microsystem, a stereo acoustic streaming tunnel, which is triggered by ultrahigh-frequency bulk acoustic waves and highly confined by a microchannel. We thoroughly analyze the generation and features of stereo acoustic streaming to develop a virtual tunnel for observation, pretreatment and analysis of cells for different single-cell applications. 3D reconstruction, dissociation of clusters, selective trapping/release, in situ analysis and pairing of single cells with barcode gel beads were demonstrated. To further verify the reliability and robustness of this technology in complex biosamples, the separation of circulating tumor cells from undiluted blood based on properties of both physics and immunity was achieved. With the rich selection of handling modes, the platform has the potential to be a full-process microsystem, from pretreatment to analysis, and used in numerous fields, such as in vitro diagnosis, high-throughput single-cell sequencing and drug development.

Accumulation of synovial fluid CD19+CD24hiCD27+ B cells was associated with bone destruction in rheumatoid arthritis.

Regulatory CD19+CD24hiCD27+ B cells were proved to be numerically decreased and functionally impaired in the peripheral blood (PB) from rheumatoid arthritis (RA), with the potential of converting into osteoclast-priming cells. However, the distribution and function of CD19+CD24hiCD27+ B cells in RA synovial fluid (SF) were unclear. In this study, we investigated whether RA SF CD19+CD24hiCD27+ B cells were increased and associated with bone destruction. We found that the proportion of RA SF CD19+CD24hiCD27+ B cells was increased significantly, and was positively correlated with swollen joint counts, tender joint counts and disease activity. CXCL12, CXCL13, CCL19 contributed to the recruitment of CD19+CD24hiCD27+ B cells in RA SF. Notably, CD19+CD24hiCD27+ B cells in the SF from RA expressed significantly more RANKL compared to OA and that in the PB from RA. Critically, RA CD19+CD24hiCD27+ B cells promoted osteoclast (OC) differentiation in vitro, and the number of OCs was higher in cultures with RA SF CD19+CD24hiCD27+ B cells than in those derived from RA PB. Collectively, these findings revealed the accumulation of CD19+CD24hiCD27+ B cells in SF and their likely contribution to joint destruction in RA. Modulating the status of CD19+CD24hiCD27+ B cells might provide novel therapeutic strategies for RA.

Rutin Attenuates Oxidative Stress and Proinflammatory Cytokine Level in Adjuvant Induced Rheumatoid Arthritis via Inhibition of NF-κB.

The present study was intended to elucidate the effect of rutin, a flavonoid, on arthritis in complete Freund's adjuvant-induced arthritic rats. The present study showed that more pronounced effect has been observed in the case of 15 mg/kg dose of rutin, with significant reduction in paw diameter together with positive modulation of hematological parameters as compared to 2 other tested doses. A significant upsurge in the level of superoxide dismutase, glutathione peroxidase and glutathione were observed together with decrease in the level of malondialdehyde after treatment with rutin in a dose-dependent manner. Furthermore, the effect of rutin on the tumor necrosis factor-α and interleukin-1ß in arthritic rats showed does-dependent lowering of these cytokines with maximum benefit at 15 mg/kg dose and the level of both NF-κB p65 and NF-κBp65 (Ser536) has been significantly reduced in the presence of rutin. Histopathological examination showed that the inflammatory cells infiltration, synovial hyperplasia, pannus formation and cartilage and bone erosion had considerably improved on administration of rutin. In conclusion, our paper strongly demonstrated the protective effect of rutin against the rheumatoid arthritis involved via suppression of NF-κB p65 protein expression.