Targeting pyroptosis with nanoparticles to alleviate neuroinflammatory for preventing secondary damage following traumatic brain injury.

Posttraumatic neuroinflammation is a key driver of secondary injury after traumatic brain injury (TBI). Pyroptosis, a proinflammatory form of programmed cell death, considerably activates strong neuroinflammation and amplifies the inflammatory response by releasing inflammatory contents. Therefore, treatments targeting pyroptosis may have beneficial effects on the treatment of secondary brain damage after TBI. Here, a cysteine-alanine-glutamine-lysine peptide-modified ß-lactoglobulin (ß-LG) nanoparticle was constructed to deliver disulfiram (DSF), C-ß-LG/DSF, to inhibit pyroptosis and decrease neuroinflammation, thereby preventing TBI-induced secondary injury. In the post-TBI mice model, C-ß-LG/DSF selectively targets the injured brain, increases DSF accumulation, and extends the time of the systemic circulation of DSF. C-ß-LG/DSF can alleviate brain edema and inflammatory response, inhibit secondary brain injury, promote learning, and improve memory recovery in mice after trauma. Therefore, this study likely provided a potential approach for reducing the secondary spread of TBI.

Multi-responsive nanofibers composite gel for local drug delivery to inhibit recurrence of glioma after operation.

BACKGROUND: The postoperative recurrence of malignant gliomas has presented a clinical conundrum currently. Worse, there is no standard treatment for these recurrent tumours. Therefore, novel promising methods of clinical treatment are urgently needed. METHODS: In this study, we synthesized reactive oxygen species (ROS)-triggered poly(propylene sulfide)60 (PPS60) mixed with matrix metalloproteinases (MMPs)-responsive triglycerol monostearate (T) lipids and TMZ. The mixed solution could self-assemble at 50 â„ƒ to generate hydrogels with MMPs- and ROS-responsiveness. We explored whether the T/PPS + TMZ hydrogel could achieve the MMP- and ROS-responsive delivery of TMZ and exert anti-glioma regrowth effects in vitro and in vivo. These results demonstrated that the T/PPS + TMZ hydrogel significantly improved the curative effect of TMZ to inhibit postsurgical recurrent glioma. RESULTS: The results confirmed the responsive release of TMZ encapsulated in the T/PPS + TMZ hydrogel, and the hydrogel showed excellent performance against glioma in an incomplete glioma operation model, which indicated that the T/PPS + TMZ hydrogel effectively inhibited the growth of recurrent glioma. CONCLUSION: In summary, we successfully developed injectable MMPs- and ROS-responsive hydrogels that could achieve the sustained release of TMZ in the surgical cavity to inhibit local recurrent glioma after surgery.

Long non-coding RNA EWSAT1 promoted metastasis and actin cytoskeleton changes via miR-24-3p sponging in osteosarcoma.

Non-coding RNAs are closely associated with tumorigenesis in multiple malignant tumours, including osteosarcoma (OS). Long non-coding RNA Ewing sarcoma-associated transcript 1 (EWSAT1) plays a role in metastasis, and actin cytoskeletal changes in OS remain unclear. In the current study, we showed that EWSAT1 expression was up-regulated in OS and that an elevation in the EWSAT1 expression level was correlated with poor prognosis in patients with OS. Functionally, we showed that knockdown of EWSAT1 suppressed migration and induced actin stress fibre degradation in MNNG/HOS and 143B cells. Moreover, we found that ROCK1 was a key downstream effector in EWSAT1-mediated cell migration and actin stress fibre changes. Furthermore, we demonstrated that ROCK1 and EWSAT1 shared a similar microRNA response element of microRNA-24-3p (miR-24-3p). Moreover, we verified that miR-24-3p suppressed ROCK1 and its mediated migration and actin stress fibres change by direct targeting. EWSAT1 promoted ROCK1-mediated migration and actin stress fibre formation through miR-24-3p sponging. Lastly, through an in vivo study, we demonstrated that EWSAT1 promoted lung metastasis in OS. According to the above-mentioned results, we suggest that EWSAT1 acts as an oncogene and that EWSAT1/miR-24-3p/ROCK1 axial could be a new target in the treatment of OS.