Structural and functional abnormalities in first-episode drug-naïve pediatric idiopathic generalized epilepsy.

The aim of this study was to investigate brain structure and corresponding static and dynamic functional connectivity (sFC & dFC) abnormalities in untreated, first-episode pediatric idiopathic generalized epilepsy (IGE), with the goal of better understanding the underlying pathological mechanisms of IGE. Thirty-one children with IGE and 31 age-matched healthy controls (HC) were recruited. Structural magnetic resonance imaging (sMRI) data were acquired, and voxel-based morphometry (VBM) analysis were performed to reveal abnormal gray matter volume (GMV). Moreover, sFC and dFC analyses were conducted using the brain areas exhibiting abnormal GMV as seed regions to explore abnormal functional couplings. Compared to HC, the IGE group exhibited increased GMV in left middle cingulate cortex (MCC) and right parahippocampus (ParaHipp). In addition, the analyses of dFC and sFC with MCC and ParaHipp as seeds revealed more extensive functional connectivity (FC) changes in dFC. Notably, the structurally and functionally abnormal brain areas were primarily localized in the default mode network (DMN). However, our study did not find any significant associations between these altered neuroimaging measurements and clinical outcomes. This study uncovered microstructural changes as well as corresponding sFC and dFC changes in patients with new-onset, untreated pediatric IGE. The affected brain regions were primarily located within the DMN, highlighting the DMN's crucial role in the development of pediatric IGE.

Is unilateral cerebellum sufficient? Insights from new cases of cerebellar agenesis and literature review.

The clinical manifestations of adult-acquired cerebellar diseases often surpass those of congenital cerebellar diseases, suggesting the significant role of the cerebellum in the developing brain. Moreover, emerging evidence from structural and functional magnetic resonance imaging indicates that the cerebellum is implicated not only in motor functions but also in non-motor domains such as cognition, emotion, and language. However, delineating the specific extent of cerebellar development required to prevent deficits in either motor or non-motor functions remains challenging. In this study, we present two new cases of unilateral cerebellar agenesis. One individual leads a nearly normal life, while the other exhibits mild cognitive impairment, mild depression, and severe autism, but maintains normal motor function. Van der Heijden et al. (2023) revealed that the brain can compensate for some, but not all, perturbations to the developing cerebellum, including motor deficits and impairments in social behaviors. Therefore, we hypothesize that comparing structural images from our patients and reviewing pertinent literature may elucidate the reasons for the varied clinical manifestations observed in patients with cerebellar agenesis.

Abnormalities of Cerebral White Matter Microstructure in Children With New-Onset, Untreated Idiopathic-Generalized Epilepsy.

Despite evidence for microstructural brain alterations in epilepsy patients, little is known about how these develop with age and the progress of the disease. The aim of this study was to investigate microstructural abnormalities of the white matter (WM) in children with new-onset, untreated idiopathic-generalized epilepsy (IGE) using the MRI technique of diffusion tensor imaging (DTI). The study was approved by the institutional review board, and all individuals or their parents gave signed informed consent. In total, 45 patients with IGE (age 5-18 years, male: female 26:19) and 32 healthy controls (HCs; age 5-18 years, male: female 21:11) were included. Voxel-based analysis (VBA) was used to compare patients and controls, and Pearson correlation analysis was used to investigate relationships between altered DTI metrics and clinical parameters. Compared with controls, patients with IGE showed increased mean diffusivity (MD) in the left splenium of the corpus callosum, increased fractional anisotropy (FA) in the right WM of the superior and middle frontal gyri, increased axial diffusivity (AD) in the WM of right corona radiata and left occipital lobe, and decreased AD in the WM of the left thalamus and the right middle cerebellar peduncle. There was no correlation between the altered diffusion parameters and clinical measures. Our study demonstrated several distinct microstructural impairments in children with new-onset, untreated IGE, of which altered AD might be the most sensitive marker of dysmyelination. The increased FA in the IGE group might suggest an initiating or compensatory mechanism that is activated prior to cognitive decline in these children.

Retracted Article: Gemcitabine aggravates miR-199a-5p-mediated breast cancer cell apoptosis by promoting VEGFA downregulation via inactivating the AKT signaling pathway.

Breast cancer is the most frequent malignancy diagnosed in women, and Gemcitabine-based therapy is frequently used to treat late-stage breast cancer. miR-199a-5p plays a tumor-suppressive role in breast cancer. This work aimed to explore the mechanism of miR-199a-5p plus Gemcitabine in breast cancer cells. Expression of miR-199a-5p was measured by RT-qPCR, while expression of vascular endothelial growth factor A (VEGFA) was measured by Western blot and RT-qPCR. Overexpression of miR-199a-5p and/or silencing of VEGFA was obtained using transfection in breast cancer cells (MCF-7 and MDA-MB-231). Functional experiments were performed to explore cell viability, apoptosis rate, and expressions of apoptosis-related genes: cell viability was assessed by MTT staining, apoptosis rate was recorded by flow cytometry, and Western blot was used to evaluate the expressions of Bcl-2, Bax and cleaved caspase 3. The signaling pathway was studied with respect to AKT activity via determination of p-AKT expression levels. Our study found that miR-199a-5p was downregulated and VEGFA was upregulated in breast cancer tissues and cells. Overexpression of miR-199a-5p and/or silencing of VEGFA contributed to cell apoptosis and inhibited cell viability, which was promoted by Gemcitabine. VEGFA was a downstream target of miR-199a-5p, and was negatively regulated by Gemcitabine. Moreover, Gemcitabine aggravated the miR-199a-5p-induced suppression of the VEGFA level and AKT activity in breast cancer cells. Our data show that Gemcitabine aggravates miR-199a-5p-mediated VEGFA downregulation and apoptosis via inactivating the AKT signaling pathway in breast cancer cells, indicating a novel promising combined therapy of miR-199a-5p overexpression and Gemcitabine.

Cortical morphologic changes in recent-onset, drug-naïve idiopathic generalized epilepsy.

PURPOSE: Only a few studies have investigated the brain morphology abnormalities in structural MRI in patients with drug-naïve idiopathic generalized epilepsy (IGE) and mainly focused on brain volume changes. In the present study, we aimed to investigate the changes in three morphologic measurement differences including cortical thickness, cortical volume, and surface area using FreeSurfer in a pediatric cohort of recent-onset, drug-naïve IGE. METHODS: Forty-five recent-onset, drug-naïve patients diagnosed with IGE and 32 demographically matched healthy controls were recruited. All participants underwent structural MRI scans with a 3.0 T MR system. FreeSurfer, an automated cortical surface reconstruction toolbox, was applied to compare the cortical morphology between patients and controls. The brain regions with significant group differences after multiple comparison correction were extracted in common space for each patient, and then correlated with their clinical characteristics (including onset age, duration of epilepsy, and mini-mental state examination (MMSE)) using partial correlation analysis with age, sex and intracranial volume as covariates. RESULTS: Compared with controls, IGE patients showed decreased cortical thickness in the left rostral middle frontal gyrus, decreased cortical volume in the right cuneus and left superior frontal gyrus that extended to the precentral gyrus, and decreased surface area in the right cuneus and right inferior parietal gyrus. None of these regions showed significant relationships with clinical measurements in the patient group. CONCLUSION: Our findings suggest that cortical thickness, cortical volume, and surface area changes occurred in the early stage of IGE. These findings provide structural neuroimaging evidence underlying the pathology of IGE.