Ginkgolide B effectively mitigates neuropathic pain by suppressing the activation of the NLRP3 inflammasome through the induction of mitophagy in rats.

Neuropathic pain is a pathological state induced by the aberrant generation of pain signals within the nervous system. Ginkgolide B(GB), an active component found of Ginkgo. biloba leaves, has neuroprotective properties. This study aimed to explore the effects of GB on neuropathic pain and its underlying mechanisms. In the in vivo study, we adopted the rat chronic constriction injury model, and the results showed that GB(4 mg/kg) treatment effectively reduced pain sensation in rats and decreased the expressions of Iba-1 (a microglia marker), NLRP3 inflammasome, and inflammatory factors, such as interleukin (IL)-1ß, in the spinal cord 7 days post-surgery. In the in vitro study, we induced microglial inflammation using lipopolysaccharide (500 ng/mL) / adenosine triphosphate (5 mM) and treated it with GB (10, 20, and 40 µM). GB upregulated the expression of mitophagy proteins, such as PINK1, Parkin, LC3 II/I, Tom20, and Beclin1, and decreased the cellular production of reactive oxygen species. Moreover, it lowered the expression of inflammation-related proteins, such as Caspase-1, IL-1ß, and NLRP3 in microglia. However, this effect was reversed by Parkin shRNA/siRNA or the autophagy inhibitor 3-methyladenine (5 mM). These findings reveal that GB alleviates neuropathic pain by mitigating neuroinflammation through the activation of PINK1-Parkin-mediated mitophagy.

Medial minimally invasive plate osteosynthesis for humeral shaft fractures: a case series.

Minimally invasive plate osteosynthesis (MIPO) is increasingly favored for treating humeral shaft fractures (HSFs). However, conventional MIPO techniques pose challenges in fixing fractures near the fossa olecrani and carry a high risk of iatrogenic radial nerve palsy. This study was aimed to report the clinical outcomes of a series of patients who underwent MIPO through a medial approach for HSFs and describe our treatment algorithm. Patients and Method: This is a study conducted in our university hospital, which is a Level 1 academic trauma center. A retrospective analysis of 21 patients with HSFs who received minimally invasive treatment using plate osteosynthesis through a medial approach over a 5-year period was conducted. The outcomes measured included time for radiographic consolidation, disabilities of the arm, shoulder, and hand score, and complications such as infection, iatrogenic radial nerve injury, loss of reduction or fixation, and nonunion. Results: Twenty-one patients who underwent the procedure were identified. Bone healing was achieved in all patients with an early and aggressive range of motion. There were no cases of infection or iatrogenic radial nerve injury. The mean radiographic fracture union time was 15.76 weeks (range: 8-40 weeks). The mean disabilities of the arm, shoulder, and hand score was 3.29 (range: 0-14.17) at the time of the last follow-up. The mean screw density was 0.43. Conclusion: The proposed algorithm is effective in addressing the challenges of iatrogenic nerve injury and extra-articular distal fixation of HSFs with conventional MIPO techniques.

Self-Amplifying Iridium(III) Photosensitizer for Ferroptosis-Mediated Immunotherapy Against Transferrin Receptor-Overexpressing Cancer.

Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene-containing Ir(III) photosensitizer (IrFc1) that can bind with transferrin and be transported into triple-negative breast cancer (TNBC) cells via a transferrin receptor-mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self-amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8+ T-cell response, which activates ICD in TNBC resulting in enhanced anticancer immunity. In summary, this work reports a small molecule-based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self-amplifying process.