Background Neuroinflammation resulting from myelin debris impedes axonal regeneration. Pharmacological modulation of myelin clearance and inflammatory responses is a potential strategy to enhance nerve regeneration. Hyperoside, a flavonoid with established anti-inflammatory and neuroprotective properties, has not been explored in peripheral nerve injury or in the context of myelin clearance. Purpose This study aims to investigate the effects and underlying mechanisms of hyperoside in promoting nerve regeneration. Methods An in vitro phagocytosis model was established in RAW264.7 macrophages with purified myelin debris. Cells were treated with hyperoside (10, 15, 30 μM). Direct hyperoside targets were identified through molecular docking and small-molecule interaction assays. Gain- and loss-of-function experiments using LPS and Stattic were performed to validate the involvement of the STAT3/ADAM17/TREM2 signaling axis. In vivo sciatic nerve crush injury models were used to examine the relationship among TREM2-mediated myelin clearance, sciatic nerve regeneration, and functional recovery. Results Hyperoside dose-dependently inhibited pro-inflammatory gene expression and apoptosis-related proteins. Mechanistically, hyperoside bound STAT3 and inhibited its phosphorylation, thereby downregulating ADAM17 and preserving TREM2-mediated myelin phagocytosis. In the sciatic nerve crush injury model, hyperoside exerted neuroprotective effects, accelerated degenerated myelin clearance, promoted nerve regeneration, and reduced muscle atrophy. Trem2 silencing impaired myelin clearance and nerve regeneration. Conclusion These findings highlight hyperoside as a promising therapeutic candidate for peripheral nerve injury. By targeting the STAT3/ADAM17/TREM2 signaling axis to enhance myelin clearance, hyperoside promotes structural and functional nerve regeneration in a rodent nerve injury model.

Background Diabetic peripheral neuropathy (DPN) represents a prevalent complication associated with diabetes mellitus, characterized by progressive nerve degeneration that leads to chronic pain and sensory dysfunction. Existing treatment options are inadequate in addressing the multifaceted underlying mechanisms of DPN, underscoring the necessity for the development of novel multitarget therapeutic strategies. Methods A systematic evaluation explored Panax ginseng's (GS) therapeutic efficacy using a multidisciplinary approach, administering the extract to diabetic rats for nerve assessments and conducting in vitro tests on Schwann cells and ND7/23 neuron cells under high glucose. Network pharmacology and molecular docking identified key targets and pathways, validated through experiments on mitochondrial function, oxidative stress, inflammation, and apoptosis. Results Administration of GS significantly improved motor nerve conduction velocity, increased pain thresholds, and restored myelination in DPN rats. In vitro, GS enhanced RSC96 and ND7/23 cell viability and migration. Network pharmacology indicated GS modulates RAGE/NF-κB and Nrf2/PPARγ pathways, reducing oxidative stress, enhancing mitochondrial function, and lowering inflammatory cytokines. It also normalizes the Bcl2/Bax ratio to mitigate apoptosis. Conclusion The findings of this study illustrate that GS mitigates DPN through a synergistic modulation of mitochondrial function, oxidative stress, neuroinflammation, and apoptosis pathways, with particularly significant effects on maintaining Schwann cell and Neuron cell functionality. Our results provide mechanistic insights that advocate for the repurposing of whole GS extract as a multitarget therapeutic agent for managing diabetic complications.

Seronegative rheumatoid arthritis (SNRA) can be a rapid-progressing and highly disabling disease. Anti-PTX3 autoantibody may be a potential biomarker in SNRA diagnosis. SNRA patients could respond well to upadacitinib.

Activation of autophagy in Schwann cells (SCs) has emerged as a powerful trigger for peripheral nerve injury (PNI) repair. Lithium ion (Li+ ) is a classical autophagy activator that plays an important role in promoting axonal extension and remyelination. However, the therapeutic window of existing lithium drugs is extremely narrow, and the adverse side effects, especially nephrotoxicity, severely limit their therapeutic value. Herein, novel Li+ -doped carbonized polymer dots (LiCPDs) was synthesized for the first time to change the pharmacokinetics of Li+ from occupying epithelial sodium channels to lipid raft-mediated endocytosis. The in-vivo results confirmed that Li-CPDs could accelerate the removal of myelin debris and promote nerve regeneration via activating autophagy of SCs. Moreover, Li-CPDs exhibited almost no renal toxicity compared to that of raw lithium drugs. Thus, LiCPDs could serve as a promising Li+ -based nanomedicine for PNI regeneration with improved biosafety.Funding Information: This work was financially supported by the National Natural Science Foundation of China (NSFC; under Grant Nos. 22035001, 21774041), the JLU Science and Technology Innovative Research Team (2017TD-06), the Jilin Provincial Department of Science and Technology Bathune Special Project (20210101360JC), and the Jilin Provincial Department of Education (JJKH20211191KJ).Declaration of Interests: The authors have declared that they have no competing interests.Ethics Approval Statement: During the experiments, the welfare of the experimental animals was fully ensured and the pain of the experimental animals was minimized as possible. The animal ethics were approved by the ethics committee from the First Hospital of Jilin University (No. 20220265).