Aims: Multiple sclerosis (MS) still maintains increasing prevalence and poor prognosis, while glucagon‐like peptide‐1 receptor (GLP‐1R) agonists show excellent neuroprotective capacities recently. Thus, we aim to evaluate whether the GLP‐1R agonist liraglutide (Lira) could ameliorate central nervous system demyelination and inflammation.Methods: The therapeutic effect of Lira was tested on experimental autoimmune encephalitis (EAE) in vivo and a microglia cell line BV2 in vitro.Results: Lira administration could ameliorate the disease score of EAE mice, delay the disease onset, ameliorate pathological demyelination and inflammation score in lumbar spinal cord, reduce pathogenic T helper cell transcription in spleen, restore phosphorylated adenosine monophosphate‐activated protein kinase (pAMPK) level, autophagy level, and inhibit pyroptosis‐related NLR family, pyrin domain‐containing protein 3 (NLRP3) pathway in lumbar spinal cord. Additionally, cell viability test, lactate dehydrogenase release test, and dead/live cell staining test for BV2 cells showed Lira could not salvage BV2 from nigericin‐induced pyroptosis significantly.Conclusion: Lira has anti‐inflammation and anti‐demyelination effect on EAE mice, and the protective effect of Lira in the EAE model may be related to regulation of pAMPK pathway, autophagy, and NLRP3 pathway. However, Lira treatment cannot significantly inhibit pyroptosis of BV2 cells in vitro. Our study provides Lira as a potential candidate for Multiple Sclerosis treatment.

Background. Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a rare form of autoimmune encephalitis caused by anti-NMDA receptor antibodies. This disease mainly affects women of childbearing age and is commonly associated with ovarian teratoma. However, the relationship between anti-NMDA receptor encephalitis and ovarian teratoma and the role of anti-NMDA receptor antibody in the relationship remain unclear. Objectives. This study aimed to describe 15 cases of anti-NMDA receptor encephalitis (5 with ovarian teratoma), review literature, and reinforce the gynecologist's knowledge of this disorder. Methods. Clinical data of 15 patients from January 2015 to December 2020 admitted to The Second Hospital of Hebei Medical University were collected and analyzed. The diagnosis of anti-NMDA receptor encephalitis was based on the presence of anti-NMDA receptor antibodies in cerebrospinal fluid (CSF) and/or serum. Laparoscopic teratoma removal was performed in patients with ovarian teratoma. All patients had received immunotherapy. In addition, a review of the literature was performed to reinforce the gynecologist's knowledge of this disorder. Results. A total of 15 patients with anti-NMDA receptor encephalitis were screened, of whom 5 patients were confirmed with ovarian teratoma by pathology. The most common symptoms of anti-NMDAR encephalitis with teratoma are fever (5/5, 100), seizure (5/5, 100), mental and behavioral disorders (4/5, 80), and decreased consciousness (4/5, 80). Conversely, the most common symptoms of patients without teratoma were neuropsychiatric symptoms, including headache (6/10, 60) and mental and behavioral disorders (7/10, 70). All patients underwent immunotherapy, including steroids, intravenous immunoglobulin (IVIG), plasma exchange, and cyclophosphamide, and 4 out of 5 patients with ovarian teratomas underwent surgical treatment. All patients had a good outcome after systemic, surgical, and immunotherapy treatment. No patient who underwent surgical treatment developed a recurrence. Conversely, 2 of 10 patients without teratoma developed an anti-NMDA receptor encephalitis recurrence. Conclusions. Patients with anti-NMDA encephalitis show severe mental and neurological symptoms. Resection of teratoma is beneficial to the relief or disappearance of symptoms and has a good prognosis. This disorder should be fully recognized by gynecologists, who play an important role in diagnosis and treatment.

Aim: This study aimed to determine the correlation between B‐lymphoid tyrosine kinase (BLK) polymorphism, mRNA gene expression of BLK, and NMOSD in a Chinese Han population.Background: B‐lymphoid tyrosine kinase gene expressed mainly in B cells plays a key role in various autoimmune disorders. However, no studies have investigated the association of BLK polymorphisms with neuromyelitis optica spectrum disorder (NMOSD).Methods: Han Chinese population of 310 subjects were recruited to analyze three single nucleotide polymorphisms (rs13277113, rs4840568, and rs2248932) under allele, genotype, and haplotype frequencies, followed by clinical characteristics stratified analysis. Real‐time PCR was used to analyze mRNA expression levels of BLK in the peripheral blood mononuclear cells of 64 subjects.Results: Patients with NMOSD showed lower frequencies of the minor allele G of rs2248932 than healthy controls (odds ratio (OR) =0.57, 95% confidence intervals (CI) 0.39–0.83, p = 0.003). The association between minor allele G of rs2248932 and reduced NMOSD susceptibility was found by applying genetic models of inheritance (codominant, dominant, and recessive) and haplotypes analysis. Subsequently, by stratification analysis for AQP4‐positivity, the minor allele G frequencies of rs2248932 in AQP4‐positive subgroup were significantly lower than in the healthy controls (OR =0.46, 95% CI 0.30–0.72, p = 0.001). Notably, the genotype GG of rs2248932 was more frequent in AQP4‐negative subgroup (n = 14) than in AQP4‐positive subgroup (n = 93) (p = 0.003, OR =0.05, 95% CI =0.01–0.57). BLK mRNA expression levels in the NMOSD patients (n = 36) were lower than in healthy controls (n = 28) (p < 0.05). However, the acute non‐treatment (n = 7), who were untreated patients in the acute phase from the NMOSD group, showed BLK mRNA expression levels 1.8‐fold higher than healthy controls (n = 8) (p < 0.05).Conclusion: This study evaluated that the minor allele G of rs2248932 in BLK is associated with reduced susceptibility to NMOSD and protected the risk of AQP4‐positive. BLK mRNA expression in NMOSD was lower as compared to healthy controls while significantly increased in acute‐untreated patients.

Background: High blood glucose is a well‐established risk factor for poor outcomes in ischemic stroke. However, the underlying molecular mechanisms linking high blood glucose to worsened stroke outcomes remain unclear. Objectives: Previous studies have implicated the NLRP3 inflammasome, a key mediator of neuroinflammation, in cerebral ischemia/reperfusion (I/R) injury. Under high blood glucose conditions, NLRP3 activation is amplified, potentially driving a vicious cycle of inflammation and neuronal death. Yet, how high blood glucose specifically modulates NLRP3 activation and its downstream pathways remains unclear. This study aimed to investigate the specific mechanisms by which high glucose enhances NLRP3 inflammasome activity and contributes to worsened brain injury following cerebral I/R. Methods: We employed a combination of in vitro and in vivo experimental approaches to explore the impact of high glucose on NLRP3 inflammasome activation and its consequences on ischemic stroke outcomes. In vitro experiments were conducted by culturing various immune cells in high‐glucose conditions to evaluate the activation of the NLRP3 inflammasome and the mitochondrial association of HK2. In vivo, mice with genetic knockouts of Nlrp3 , Pycard (the gene encoding ASC), or microglial‐specific Hk2 were subjected to transient middle cerebral artery occlusion (tMCAO). Results: Our findings revealed that the activation of the NLRP3 inflammasome was enhanced post cerebral I/R under high glucose and a N‐terminal truncation of NLRP3 (miniNLRP3) was induced. Overexpression of PKA could promote the generation of miniNLRP3, while inhibition of PKA decreased the generation of miniNLRP3. In addition, treatment with pan serine protease could block PKA and LPS mediated generation of miniNLRP3. Overexpression of the N‐terminal truncation of NLRP3 could potentiate the activation of the NLRP3 inflammasome under high glucose conditions by promoting the dissociation of Hexokinase 2 (HK2) from mitochondria. In addition, knockout of Nlrp3 , Pycard , or microglial Hk2 , could all attenuate cerebral I/R‐induced brain injury under high blood glucose in mice. Conclusion: Our study elucidates PKA‐mediated generation of a 30 kD N‐terminal truncation of NLRP3 (miniNLRP3) in a serine protease‐dependent manner, which could potentiate the activation of the NLRP3 inflammasome under high glucose conditions via promoting the dissociation of HK2 from mitochondria. These findings add a new dimension to our understanding of NLRP3 regulation in the context of stroke injury, and suggest that the PKA‐miniNLRP3‐HK2‐NLRP3 pathway is a promising therapeutic strategy to improve stroke outcomes in patients with elevated blood glucose levels.