Neuroprotective effect of alpha-kinase 1 knockdown against cerebral ischemia through inhibition of the NF-κB pathway and neuroinflammation.

BACKGROUND: Activation of the nuclear factor B (NF-κB) signaling pathway by pattern recognition receptors (PRRs) is regarded as a crucial mechanism of neuroinflammation and brain injury after acute ischemic stroke. The stimulation of alpha-kinase 1 (ALPK1), a newly identified PRR, triggers NF-κB activation and an inflammatory response. Longitudinal population-based genetic epidemiological studies suggest that the ALPK1 gene is a susceptible site to ischemic stroke. However, the function of ALPK1 in the central nervous system remains unclear. The present study explored the role of ALPK1 in acute ischemic stroke. METHODS: BV2 microglial cells were stimulated with conditioned medium (CM) that was collected from oxygen and glucose deprivation (OGD)-treated HT22 neurons, and a murine brain ischemia model was established to detect the changes of ALPK1 expression. We used lentivirus to knockdown ALPK1 to explore the effects of ALPK1 in cerebral ischemia models in vitro and in vivo. RESULTS: We observed a significant increase of ALPK1 expression in BV2 cells that were stimulated with OGD CM. The knockdown of ALPK1 inhibited the phosphorylation of tumor necrosis factor receptor associated factor-interacting protein with a forkhead-associated domain (TIFA), the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), the activation of NF-κB, and the levels of proinflammatory factors in the BV2 cells. We also verified a neuroprotective effect of ALPK1 knockdown against ischemic brain injury through inhibition of the TIFA/TRAF6/NF-κB pathway and neuroinflammation in mice. CONCLUSIONS: This study demonstrates that ALPK1 is implicated in sterile inflammatory injury after acute brain ischemia, which provides first evidence for the therapeutic potential of ALPK1 inhibition in ischemic stroke.

Analysis of the Efficacy and Safety of Pulpitis Treated with Different Root Canal Flushing Fluids Based on VAS and Temporomandibular Joint Function.

Pulpitis is one of the common diseases indicated by the department of stomatology that is located in the tooth and contains abundant nerve vessels. In order to evaluate the pain degree and functional recovery of patients after treatment by visual analogue pain scale (VAS) and temporomandibular joint function score, a retrospective analysis was performed on 128 patients diagnosed with pulpitis who received root canal treatment in the department of stomatology from January 2020 to March 2021. The results show that 3%NaClO combined with 0.9% sodium chloride injection can effectively relieve the pain degree of patients after treatment, and the antibacterial effect is significantly better than 3%H2O2 combined with 0.9% normal saline. Meanwhile, it can effectively improve the temporomandibular joint function and reduce the recurrence rate, which has good clinical application value.