Exploring brain network oscillations during seizures in drug-naïve patients with juvenile absence epilepsy.

Objective: We aimed to investigate the brain network activity during seizures in patients with untreated juvenile absence epilepsy. Methods: Thirty-six juvenile absence epilepsy (JAE) patients with a current high frequency of seizures (more than five seizures during a 2 h EEG examination) were included. Each participant underwent a 2 h video EEG examination. Five 10 s EEG epochs for inter-ictal, pre-ictal, and post-ictal, and five 5 s EEG epochs for ictal states were extracted. Five 10 s resting-state EEG epochs for each participant from a sex- and age-matched healthy control (HC) were enrolled. The topological parameters of the brain networks were calculated using a graph theory analysis. Results: Compared with the resting state of the HC group, the global efficiency, local efficiency, and clustering coefficients of the JAE group decreased in the inter-ictal state. In addition, the ictal state showed significantly increased global and local efficiency and clustering coefficients (p < 0.05) and a decreased small-world index and the shortest path length (p < 0.05) in the theta and alpha bands, compared to the remaining states within the JAE group. Moreover, subgroup analysis revealed that those JAE patients with typical 3 Hz discharges had upgraded global efficiency, local efficiency, and clustering coefficients in both delta and beta1 bands, compared to those JAE patients with non-3 Hz discharges during seizures. Conclusion: The present study supported the idea that the changes in the EEG brain networks in JAE patients are characterized by decreased global and local efficiency and clustering coefficient in the alpha band. Moreover, the onset of seizures is accompanied by excessively enhanced network efficiency. JAE patients with different ictal discharge patterns may have different functional network oscillations.

Tilianin improves cognition in a vascular dementia rodent model by targeting miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways.

Introduction: Although vascular dementia (VaD) is the second most prevalent form of dementia, there is currently a lack of effective treatments. Tilianin, isolated from the traditional drug Dracocephalum moldavica L., may protect against ischemic injury by inhibiting oxidative stress and inflammation via the CaMKII-related pathways but with weak affinity with the CaMKII molecule. microRNAs (miRNAs), functioning in post-transcriptional regulation of gene expression, may play a role in the pathological process of VaD via cognitive impairment, neuroinflammatory response, and neuronal dysfunction. This study aimed to investigate the role of tilianin in VaD therapy and the underlying mechanism through which tilianin regulates CaMKII signaling pathways based on miRNA-associated transcriptional action. Methods: Rats with 2-vessel occlusion (2VO), a standard model of VaD, were treated with tilianin, vehicle control, and target overexpression or downregulation. High-throughput sequencing, qRT-PCR, and western blot analyses were utilized to identify the downstream target genes and signaling pathways of tilianin involved in VaD. Results: Our results showed that tilianin ameliorated cognitive deficits, neurodegeneration, and microglial and astrocytic activation in rats with 2VO. Subsequent high-throughput sequencing and qRT-PCR analyses revealed that tilianin increased the downregulated miR-193b-3p and miR-152-3p levels in the cortex and hippocampus of 2VO rats. Mechanistically, miR-193b-3p targeting CaM and miR-152-3p targeting CaMKIIα were identified to play a role in VaD-associated pathology, inhibiting the p38 MAPK/NF--κB p65 pathway and decreasing TNF-α and IL-6 levels. Further gain- and loss-of-function experiments for these key genes showed that tilianin-exerted cognitive improvement by activating the p38 MAPK/NF--κB p65 and Bcl-2/Bax/caspase-3/PARP pathways in the brain of 2VO rats was abolished by miR-193b-3p and miR-152-3p inhibition. Moreover, CaM and CaMKIIα overexpression eliminated the elevated effects of miR-193b-3p and miR-152-3p on tilianin's protection against ischemic injury through increased inflammatory reactions and apoptotic signaling. Discussion: Together, these findings indicate that tilianin improves cognition by regulating the miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways, suggesting a potential small-molecule regulator of miRNA associated with inflammatory signaling for VaD treatment.

Neural oscillations after acute large artery atherosclerotic cerebral infarction during resting state and sleep spindles.

Electroencephalogram-microstate analysis was conducted using low-resolution electromagnetic tomography (LORETA)-KEY to evaluate dynamic brain network changes in patients with acute large artery atherosclerotic cerebral infarction (LAACI) during the rest and sleep stages. This study included 35 age- and sex-matched healthy controls and 34 patients with acute LAACI. Each participant performed a 3-h, 19-channel video electroencephalogram test. Subsequently, 20 epochs of 2-s sleep spindles during stage N2 sleep and five epochs of 10-s electroencephalogram data in the resting state for each participant were obtained. In both the resting state and sleep spindles, patients with LAACI displayed altered neural oscillations. The parameters of microstate A (coverage, occurrence, and duration) increased during the resting state in the patients with LAACI compared with healthy controls. The coverage and occurrence of microstate B and D were reduced in the LAACI group compared with the healthy controls (p < 0.05). Moreover, during sleep spindles, the duration of microstate A and the transition probability from microstate A and B to C decreased, but the coverage of microstate B and the transition rate from microstate B to D increased (p < 0.05) in the LAACI group compared with the healthy controls. These results enable better understanding of how neural oscillations are modified in patients with LAACI during the resting state and sleep spindles. Following LAACI, the dynamic brain network undergoes changes during sleep spindles and the resting state. Continued long-term investigations are required to determine how well these changes in brain dynamics reflect the clinical characteristics of patients with LAACI.

Spatio-temporal dynamics of resting-state brain networks are associated with migraine disability.

OBJECTIVE: The changes in resting-state functional networks and their correlations with clinical traits remain to be clarified in migraine. Here we aim to investigate the brain spatio-temporal dynamics of resting-state networks and their possible correlations with the clinical traits in migraine. METHODS: Twenty Four migraine patients without aura and 26 healthy controls (HC) were enrolled. Each included subject underwent a resting-state EEG and echo planar imaging examination. The disability of migraine patients was evaluated by Migraine Disability Assessment (MIDAS). After data acquisition, EEG microstates (Ms) combining functional connectivity (FC) analysis based on Schafer 400-seven network atlas were performed. Then, the correlation between obtained parameters and clinical traits was investigated. RESULTS: Compared with HC group, the brain temporal dynamics depicted by microstates showed significantly increased activity in functional networks involving MsB and decreased activity in functional networks involving MsD; The spatial dynamics were featured by decreased intra-network FC within the executive control network( ECN) and inter-network FC between dorsal attention network (DAN) and ECN (P < 0.05); Moreover, correlation analysis showed that the MIDAS score was positively correlated with the coverage and duration of MsC, and negatively correlated with the occurrence of MsA; The FC within default mode network (DMN), and the inter-FC of ECN- visual network (VN), ECN- limbic network, VN-limbic network was negatively correlated with MIDAS. However, the FC of DMN-ECN was positively correlated with MIDAS; Furthermore, significant interactions between the temporal and spatial dynamics were also obtained. CONCLUSIONS: Our study confirmed the notion that altered spatio-temporal dynamics exist in migraine patients during resting-state. And the temporal dynamics, the spatial changes and the clinical traits such as migraine disability interact with each other. The spatio-temporal dynamics obtained from EEG microstate and fMRI FC analyses may be potential biomarkers for migraine and with a huge potential to change future clinical practice in migraine.

One-pot synthesis of oxoaporphines as potent antitumor agents and investigation of their mechanisms of actions.

An efficient one-pot reaction for the synthesis of oxoaporphine alkaloids has been developed. Twenty-three compounds of oxoaporphine alkaloids were prepared and assessed for their antitumor activities. Most compounds inhibited the growth of T-24 tumor cells in vitro. Particularly, 4B displayed the most potent activity with an IC50 value of 0.5 µM, which was 19-fold more potent than the parent compound 4. The substitution at C3-position of oxoaporphine core by -NO2 significantly enhanced the anticancer activity. Mechanism studies indicated that 4 and 4B induced cell cycle arrest at G2/M phase; in contrast, 4V induced cell cycle arrest at the S phase. Increase of mitochondrial ROS/Ca2+ and decrease of MMP, accompanied by activation of caspase-3/9, were observed in T-24 cells after exposure to compounds 4, 4B and 4V, suggesting that the mitochondrial pathway was involved in the induced apoptosis. Moreover, compound 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24.