Osteoarthritis (OA) is a highly prevalent and chronic disorder that is associated with a substantial social and economic burden. Itaconate, as an important regulator of cellular inflammation, is a metabolite synthesised by an enzyme encoded by immune-responsive gene 1. However, there are few studys regarding the effects of itaconate on OA. Here, we show the effect of the cell-permeable itaconate derivative 4-octyl itaconate (OI) on OA. OI attenuates the chondrocyte apoptosis induced by interleukin 1β (IL-1β) in vitro, indicating that OI protect chondrocytes against apoptosis. Moreover, OI ameliorates the chondrocyte autophagy inhibition induced by IL-1β via the inhibition of PI3K/AKT/mTOR signalling pathway. Finally, OI enhances autophagy and reduces cartilage degradation in a rat model of OA established by destabilization of medial meniscus (DMM). In summary, our findings reveal that OI is involved in regulating the progression of OA. The above results shed light on the treatment of OA.
Objective
The aim of this meta‐analysis was to systematically evaluate the efficacy of augmentative plating (AP) and exchange nailing (EN) in the treatment of nonunion of femoral shaft fracture.
Methods
For the present meta‐analysis, PubMed, EMBASE, and the Cochrane Library were searched to identify relevant articles up to April 2019. Two investigators independently evaluated the quality of original publications following the guidelines proposed by the Cochrane Handbook. Data were extracted from the studies and analyzed using Review Manager 5.3.
Results
Five studies were included in this meta‐analysis, with a total of 506 patients. There were 232 patients in the AP group and 276 patients in the EN group. The AP group was associated with higher union rate (OR, 11.66; 95% CI, 4.31–31.50; P < 0.01), shorter union time (SMD, −1.10; 95% CI, −2.09 to −0.11; P = 0.03), shorter operation time (SMD, −0.55; 95% CI, −0.88 to −0.21; P < 0.01), less blood loss (SMD, −1.72; 95% CI, −3.33 to −0.11; P < 0.01), and fewer complications (OR, −0.11; 95% CI, −0.16 to −0.07; P < 0.01) than the EN group.
Conclusion
The results of the meta‐analysis showed that AP is found to be superior for nonunion of femoral shaft fractures in both intraoperatively (ie, shorter operation time and less blood loss) and postoperatively (ie, higher union rate, shorter union time, and lower complication rate). Overall, AP was superior to EN in the treatment of nonunion of femoral shaft fractures after intramedullary nailing (IMN).
The scaffold structures formed by the incorporation of reduced graphene oxide (RGO) nanomaterials can be studied to improve the 3D matrix properties in the applications of bone regeneration. On the other hand, RGO has delayed the incorporation into the mixtures that were determined to generate scaffolds on using 3D printing because of its poor colloidal stability of particles and weak solubility in water. Moreover, to produce RGO, the graphene oxide (GO) was treated with hydrazine hydrate solution, which was well known as a reducing agent that is highly hazardous. To outcome these drawbacks, an unique eco-friendly method was established to gather scaffolds that were 3D printed by the incorporation of RGO. This was obtained using the Gallic acid induced in situ reduction of the GO already existing on the gelatin/chitosan/tricalcium phosphate scaffolds. Moreover, scaffolds also exhibited antibacterial activity without conceding osteoblasts' cell proliferation and viability. Furthermore, the obtained scaffolds showed good osteoblasts proliferation and viability indicating their possibility for applications in bone fracture healing.
Treatment of osteoarthritis (OA) remains a significant clinical challenge. Itaconate (IA), an emerging regulator of intracellular inflammation and oxidative stress, may potentially be harnessed to treat OA. However, the short joint residence time, inefficient drug delivery, and cell-impermeable property of IA can seriously hamper the clinical translation. Herein, IA-encapsulated zeolitic imidazolate framework-8 (IA-ZIF-8) nanoparticles were self-assembled by zinc ions, 2-methylimidazole, and IA to render them pH-responsive. Subsequently, IA-ZIF-8 nanoparticles were firmly immobilized in hydrogel microspheres via one-step microfluidic technology. It was demonstrated in vitro experiments that IA-ZIF-8-loaded hydrogel microspheres (IA-ZIF-8@HMs) exhibited good anti-inflammatory and anti-oxidative stress effects by releasing pH-responsive nanoparticles into chondrocytes. Importantly, compared with IA-ZIF-8, IA-ZIF-8@HMs showed better performance in the treatment of OA due to their superior performance in sustained release. Thus, such hydrogel microspheres not only hold enormous potential for OA therapy, but also provide a novel avenue for cell-impermeable drugs by constructing appropriate drug delivery systems.
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