ABSTRACT
Objectives: The network mechanism underlying the initial response to antiseizure medication in epilepsy has not been revealed yet. Given the central role of the thalamus in the brain network, we conducted a case-control study to investigate the association between thalamic connectivity and medication response. Methods: We recruited 39 patients with newly diagnosed and medication-naïve epilepsy of genetic or unknown etiology, including 26 with a good response (GR group) and 13 with a poor response (PR group), and 26 matched healthy participants (control group). We measured the gray matter density (GMD) and the amplitude of low-frequency fluctuation (ALFF) of bilateral thalami. We then set each thalamus as the seed region of interest (ROI) to calculate voxel-wise functional connectivity (FC) and assessed ROI-wise effective connectivity (EC) between the thalamus and targeted regions. Results: We found no significant difference between groups in the GMD or ALFF of bilateral thalami. However, we observed that the FC values of several circuits connecting the left thalamus and the cortical areas, including the bilateral Rolandic operculum, the left insula, the left postcentral gyrus, the left supramarginal gyrus, and the left superior temporal gyrus, differed among groups (False Discovery Rate correction, P < 0.05), with a higher value in the PR group than in the GR group and/or the control group (Bonferroni correction, P < 0.05). Similarly, both the outflow and the inflow EC in each thalamocortical circuit were higher in the PR group than in the GR group and the control group, although these differences did not remain statistically significant after applying the Bonferroni correction (P < 0.05). The FC showed a positive correlation with the corresponding outflow and inflow ECs for each circuit. Conclusion: Our finding suggested that patients with stronger thalamocortical connectivity, potentially driven by both thalamic outflowing and inflowing information, may be more likely to respond poorly to initial antiseizure medication.
ABSTRACT
Diabetic cardiomyopathy (DCM) is a common heart disease. The Phase II enzyme inducer (CPDT) is a complex enzyme that promotes the expression of antioxidant enzymes through activating nuclear factor erythroid 2-related factor 2 (Nrf2); these compounds have been shown to protect against oxidative stress. However, whether these compounds have similar protective effects in DCM still remains unclear. The purpose of this study is to investigate the protective effects and potential mechanism of CPDT in diabetic cardiomyopathy. In the results, firstly, compared with control rats, myocardial cell size, left ventricular mass index, and myocardial apoptosis index were increased, miR-503 was increased, and Nrf2, malondialdehyde (MDA), and heme oxygenase 1 (HO-1) were decreased in diabetic cardiomyopathy rats. Furthermore, compared with diabetic cardiomyopathy rats, these above parameters show the opposite change in CPDT treatment rats. In addition, the bioinformatics and luciferase reporter assay demonstrated that Nrf2 is a direct target of miR-503. Finally, the miR-503 could also regulate Nrf2 in the myocardial cells. Therefore, miR-503 is involved in the protective effect of CPDT in diabetic cardiomyopathy via Nrf2/ARE signaling pathway; miR-503 and Nrf2 may be a promising therapeutic target for the management of diabetic cardiomyopathy.
