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.

This study aims to assess the diagnostic efficacy of a novel integrated approach that combines a modified percutaneous disc biopsy technique with 16 S rRNA gene sequencing to enhance pathogen identification in patients with early suspected pyogenic spondylodiscitis (PS). A retrospective cohort study was conducted, enrolling 66 patients who underwent percutaneous biopsy based on clinical and MRI findings indicative of early PS between January 2021 and January 2024. Patients were categorized into two groups: Group A (n = 31), which received traditional transpedicular biopsy coupled with 16 S rRNA gene sequencing, and Group B (n = 35), which received the modified transpedicular-vertebral-discal biopsy combined with genetic testing. A composite follow-up, including clinical symptoms, imaging, and laboratory findings at ≥ 6 months, served as the gold standard. Pathogen detection rates, complication rates, and pathogen profiles were compared between the groups. Baseline characteristics were comparable between the groups. The pathogen detection rate in Group B (85.7%, 30/35) was significantly higher than that in Group A (51.6%, 16/31), with a statistically significant difference (P < 0.01). No serious procedure-related complications were observed in either group. The predominant infection in both groups was monomicrobial bacterial infection, with Staphylococcus aureus identified as the most common pathogen. The modified percutaneous biopsy technique combined with 16 S rRNA gene sequencing significantly improves pathogen detection in early pyogenic spondylodiscitis without increasing the risk of complications. This integrated approach demonstrates substantial diagnostic value and shows promise as a first-line minimally invasive diagnostic method.

The role of oxidative stress and ferroptosis in the pathogenesis of osteoarthritis (OA) is significant. 4-Octyl Itaconate (OI) has been shown to have protective effects against oxidative stress and inflammatory response, and has been identified as a potential therapeutic agent for OA. However, the specific effects of OI on the regulation of chondrocyte degeneration, oxidative stress, and ferroptosis require further investigation. The objective of our study was to examine the effects of OI on IL-1β-induced chondrocytes and an OA mouse model. Our results demonstrate that OI effectively mitigates IL-1β-induced chondrocyte degeneration in a dose-dependent manner. Additionally, OI exhibited a significant inhibitory effect on ROS production and mitigated the decline in Recombinant Glutathione Peroxidase 4 (GPX4) levels induced by IL-1β and Erastin, a ferroptosis activator. As a result, OI demonstrated potential in attenuating the degenerative effects of IL-1β and Erastin on chondrocytes, possibly through the reduction of ferroptosis. The molecular mechanism underlying OI's regulation of GPX4 expression in chondrocytes was found to involve the repression of GPX4 methylation. Furthermore, the inhibition of GPX4 methylation was observed to improve IL-1β-triggered degeneration, oxidative stress, and ferroptosis in chondrocytes. Comparable outcomes were obtained in animal models of osteoarthritis (OA). The utilization of OI and Ferrostatin-1 (Fer-1) mitigated the progression of OA and cartilage degeneration in the mouse model of OA, which was established by destabilization of medial meniscus (DMM). Consequently, it can be inferred that OI alleviates degeneration, oxidative stress, and ferroptosis in IL-1β-treated chondrocytes by inhibiting GPX4 methylation bothin vitroandin vivo. These findings indicate that OI represents a promising new therapeutic modality for OA.