ABSTRACT
Status epilepticus (SE) is a life-threatening disorder that can result in death or severe brain damage, and there is a substantial body of evidence suggesting a strong association between pyroptosis and SE. Sterol regulatory element binding protein 1 (SREBP1) is a significant transcription factor participating in both lipid homeostasis and glucose metabolism. However, the function of SREBP1 in pyroptosis during SE remains unknown. In this study, we established a SE rat model by intraperitoneal injection of lithium chloride and pilocarpine in vivo. Additionally, we treated HT22 hippocampal cells with glutamate to create neuronal injury models in vitro. Our results demonstrated a significant induction of SREBP1, inflammasomes, and pyroptosis in the hippocampus of SE rats and glutamate-treated HT22 cells. Moreover, we found that SREBP1 is regulated by the mTOR signaling pathway, and inhibiting mTOR signaling contributed to the amelioration of SE-induced hippocampal neuron pyroptosis, accompanied by a reduction in SREBP1 expression. Furthermore, we conducted siRNA-mediated knockdown of SREBP1 in HT22 cells and observed a significant reversal of glutamate-induced cell death, activation of inflammasomes, and pyroptosis. Importantly, our confocal immunofluorescence analysis revealed the co-localization of SREBP1 and NLRP1. In conclusion, our findings suggest that deficiency of SREBP1 attenuates glutamate-induced HT22 cell injury and hippocampal neuronal pyroptosis in rats following SE. Targeting SREBP1 may hold promise as a therapeutic strategy for SE.
ABSTRACT
Purpose: Hepatitis E virus infection mainly presents with liver-related symptoms, and multiple studies have shown that hepatitis E virus infection can also induce extrahepatic-related symptoms. Thrombotic thrombocytopenic purpura is an uncommon and fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ damage, and microangiopathic haemolytic anaemia. We report the first case in which acute hepatitis E induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Patients and Methods: A 53-year-old male was admitted to our emergency department with fever, thrombocytopenia, and abnormal liver function. Laboratory tests revealed significant bilirubin, AST, and ALT elevations, renal impairment, positive anti-HEV IgM and IgG antibody results, schistocytes on the blood smear, 0% ADAMTS-13 activity, and positive ADAMTS13 inhibitor results. He was diagnosed with acute hepatitis E, which induced the first episode of immune-mediated thrombotic thrombocytopenic purpura. Results: After receiving treatment with plasmapheresis, glucocorticoid medication, rituximab, and other supportive medicines, the patient's physiological circumstances and laboratory indicators improved, and a 4-month follow-up revealed no abnormalities. Conclusion: This is a unique case report of an acute hepatitis E-induced immune-mediated thrombotic thrombocytopenic purpura initial episode. This case report offers evidence that hepatitis E virus infection can cause thrombotic thrombocytopenic purpura. In patients with abnormal liver function and thrombocytopenia, we advise screening for hepatitis E or thrombotic thrombocytopenic purpura.
ABSTRACT
OBJECTIVE: To detect the Calpain10 gene polymorphisms in North China families with type 2 diabetes and to investigate their association with type 2 diabetes. METHODS: PCR-RFLP method was used to test the polymorphisms of Calpain10 SNP43 (G/A) and SNP19 (1/2) in 801 individuals from 218 type 2 diabetes mellitus (DM) families, 211 type 2 diabetes patients without family history, and 127 normal control subjects in northern China. RESULTS: (1) The Calpain 10 SNP43 "G" allele frequency was 91.9% in the type 2 diabetic patients without family history, 92.7% in the probands from the type 2 diabetes families without linkage between the onset of DM and SNP43 site, and 95.3% in the probands from type 2 diabetes families with linkage evidence at SNP43, all significantly higher than that in the controls (85.8%, chi(2) = 6.39, df = 1,P = 0.011; chi(2) = 8.437,df = 1, P < 0.01); and chi(2) = 16.49, df = 1, P < 0.01). The distribution of polymorphism of the SNP19 site was not significantly different between the patients and control subjects. (2) Logistic regression analysis adjusted by BMI, sex and age showed that SNP43 G/G genotype was associated with type 2 diabetes. The odds ratios of the three group were OR = 1.78, P = 0.045; OR = 2.53, P = 0.008; OR = 4.32, P = 0.000 respectively. CONCLUSION: SNP43 site of Calpain10 gene is related to type 2 diabetes. Calpain 10 gene may be a related gene of type 2 diabetes in Chinese.
