TRIM32 Inhibits NEK7 Ubiquitylation-Dependent Microglia Pyroptosis After Spinal Cord Injury.

Spinal cord injury (SCI) is a disabling disease associated with microglial activation. Tripartite motif containing 32 (TRIM32) is an E3 ubiquitin ligase that plays a role in SCI. This study aimed to explore the role of TRIM32 in SCI and its potential mechanisms. We established an SCI mouse model to assess the function of TRIM32 using quantitative real-time polymerase chain reaction (qPCR), and hematoxylin and eosin staining. Additionally, a lipopolysaccharides (LPS)-induced cell injury model was generated to explore the impact of TRIM32 on pyroptosis using qPCR, propidium iodide staining, and western blotting. The ubiquitylation of NEK7 was analyzed using western blotting, co-immunoprecipitation, and immunofluorescence staining. The results showed that TRIM32 expression was increased in SCI mice and LPS-induced BV-2 cells. Overexpression of TRIM32 ameliorated SCI in mice and suppressed pyroptosis in LPS-treated BV-2 cells. Additionally, the E3 ligase TRIM32 promoted the ubiquitylation of NEK7 at the K64 site, leading to the downregulation of NEK7 levels. Inhibiting NEK7 ubiquitylation reversed the suppression of pyroptosis by TRIM32. In conclusion, TRIM32 inhibits microglia pyroptosis by facilitating the ubiquitylation of NEK7 at the K64 site, thereby alleviating the progression of SCI. The findings suggest that TRIM32 has the potential to be a therapeutic target of SCI.

Analysis of the Effect of Percutaneous Cone Shaping in Patients with Osteoporotic Vertebral Fractures.

Objective: To study and analyze the clinical effect of percutaneous cone shaping in patients with osteoporotic vertebral fractures. Methods: A total of 100 patients with vertebral osteoporotic fracture treated in our hospital from June 2019 to September 2020 were selected, and there were 50 patients with vertebral osteoporotic fracture in each group. Patients could be divided into two groups according to different treatment plans: one group was vertebroplasty patients for group A, and the other group was nonsurgical treatment patients for group B. The incidence of complications during treatment and follow-up was recorded in both groups. Results: According to a study, both groups of patients completed the treatment and follow-up, no patients lost to follow-up or death, the VAS scores and ADL scores of patients before treatment were higher, and there was no significant difference at baseline (P > 0.05). After different treatment methods, the VAS score and ADL score of group A showed good improvement after treatment compared with that before treatment, and there were certain differences within the group, with statistical significance (P < 0.05). Intragroup comparison. The VAS scores of group B at 1 week, 1 month, 3 months, and 12 months after treatment were all superior to those before treatment, and the ADL scores at 1 month, 3 months, and 12 months after treatment were all superior to those before treatment, with statistically significant differences (P < 0.05). VAS scores and ADL scores showed good improvement 1 day, 1 week, and 1 month after treatment compared with those before treatment. However, there were no significant differences in the VAS score and ADL score between the two groups at 3 and 12 months after treatment. The incidence of complications in group A is lower than that in group B. The incidence of complications in group A is as follows: there was 1 case of recurrent vertebral fracture and 1 case of urinary tract infection, and the overall incidence of complications was 4.00%. In group B, there were 1 case of recurrent fracture, 3 cases of bedsore, 2 cases of urinary tract infection, and 2 cases of pulmonary infection, and the incidence of total complications was 16.00%. After comparison between groups, there was a significant difference in the incidence of complications between the two groups, and the difference was statistically significant (P < 0.05). Conclusions: Percutaneous cone plasty can provide rapid relief of pain symptoms in patients with osteoporotic vertebral fractures and significantly improve their daily activities. However, there was no significant difference in long-term recovery from group B. In terms of the incidence of complications, the incidence of complications in group A was lower than that in group B after certain treatment.

Effect of Intraarticular Injection of Platelet-Rich Plasma on Knee Osteoarthritis: A Multicenter Retrospective Clinical Study.

This study aimed to evaluate the effect of intraarticular injection with platelet-rich plasma on knee osteoarthritis. A total of 250 patients with stages I-III osteoarthritis from December 2018 to June 2020 were included in this study. All the patients had received autologous PRP injection (3 ml) into the affected knee joint every week for totally 3 injections. The VAS score and WOMAC index were used to evaluate knee function before and at 3 days, 1 month, and 3 months after injection. A total of 250 patients were enrolled in this study, including 130 patients in the PRP group and 120 patients in the control group. The content of platelets in PRP of patients in the PRP group was 958.0 ± 283.1 × 109/L. The VAS score and WOMAC index of patients in the PRP group before treatment were not significantly different from those in the control group. At 3 days, 1 month, and 3 months after PRP treatment, the VAS score and WOMAC index of the PRP group were significantly lower than those of the control group. PRP is effective in treatment of knee osteoarthritis. The pain symptoms can be alleviated at 3 days after injection.

Inhibiting RGS1 attenuates secondary inflammation response and tissue degradation via the TLR/TRIF/NF-κB pathway in macrophage post spinal cord injury.

Macrophage-dominated inflammation by the activation of Toll-like receptor (TLR) pathway leads to neurological disruption after spinal cord injury (SCI). Regulator of G-protein signaling 1 (RGS1) is reported to be a regulator in inflammation. The present study thus purposes to identify the unknown role of RGS1 mediating TLR on inflammation post SCI. A mouse model of traumatic SCI was established by a mechanical trauma at T10. The mice underwent SCI and a macrophage line activated by lipopolysaccharide (LPS) were treated with shRNA-RGS1 to elucidate the role of RGS1 in inflammatory progression. The inflammatory factors were measured, and the degree of histology and function protection were determined. The expression levels of RGS1, myeloid differentiation primary response protein 88 (Myd88), (TIR-domain-containing adaptor inducing interferon-ß (TRIF), p38, metalloproteinase (MMP)-2, and MMP-9 were determined. RGS1 was robustly increased both in LPS-activated macrophage and SCI mice. The TLR signaling pathway-induced inflammation was suppressed by RGS1 knockdown. shRNA-mediated silence of RGS1 was exhibited a prominent decrease in TNF-α, IL-1ß and IL-6 via TLR/TRIF/ nuclear factor kappa-B (NF-κB) axis. Depletion of RGS1 also inhibited MMP-induced tissue degradation via MAPK-p38 pathway in SCI mice. Moreover, suppression of RGS1 improved spinal cord histology and function recovery. These findings suggest that RGS1 regulates inflammation and tissue disruption via TLR/TRIF/NF-κB signaling pathway in mice with SCI, thereby explaining a novel target that regulates macrophage inflammation post SCI.