Cellular and Molecular Neurobiology最新文献

The kallikrein-kinin system (KKS) plays a key role in inflammatory responses, but its specific contribution to neuroinflammation remains to be fully elucidated. The bradykinin B₂ receptor (B₂R), a principal effector of the KKS, is widely expressed in both neuronal and glial cells in the rodent and human brain. In this study, we investigated the molecular contribution of B₂R to neuroinflammation using complementary in vitro and in vivo models. Lipopolysaccharide (LPS) stimulation significantly upregulated B₂R mRNA expression in primary astrocyte cultures and in the cortical tissue of wild-type mice. Pharmacological blockade of B₂R in astrocytes markedly suppressed the LPS-induced proinflammatory gene expression. In contrast, B₂R antagonism in vivo resulted in only partial attenuation of the neuroinflammatory response. Together, these findings suggest cell type-specific roles for B₂R and underscore its key contribution to astrocyte-mediated neuroinflammation.

The administration of anaesthesia during pregnancy may have implications for fetal brain development. This study used H1 embryonic stem cell-derived human brain organoids (HBOs) to investigate effects of intermittent propofol exposure (IPE). HBOs were subjected to early IPE from 47 to 50 days in vitro (div), or late IPE from 77 to 80 div, using a clinically supra-anaesthetic concentration of 50 µM propofol. This was followed by cultivation without propofol for an additional 10 div, and HBOs were subsequently analysed at 60 or 90 div. Determination of HBO growth and lactate release did not provide evidence of neurotoxicity. Multi-electrode array recordings indicated an increased neuronal activity at 60 div following early IPE, an effect not observed at 90 div following late IPE. RNA-sequencing revealed that IPE up-regulated genes associated with neurodevelopment and synapse functions at 60 div, which overlapped with naturally up-regulated genes during HBO development from 60 to 90 div. These findings indicate that early IPE accelerates brain maturation in HBOs, suggesting possible deviations from the normal developmental trajectory in the fetal brain.

Ferroptosis, a novel form of cell death primarily characterized by iron overload and lipid peroxidation, differs from traditional apoptosis and is finely regulated by multiple mechanisms. Recent studies have demonstrated that ferroptosis plays vital roles in the onset and progression of cancers, cardiovascular, and neurological diseases. There are several spine-related diseases that affect the bones, limbs, and nervous system, such as spinal cord injuries and intervertebral disc degeneration. With the advancement in research, increasing evidence suggests that ferroptosis plays a role in these conditions and affects their treatment. This review outlines the mechanisms of ferroptosis and discusses the recently reported ferroptotic mechanisms associated with spinal cord injuries and intervertebral disc degeneration. Additionally, it emphasizes the necessity for further research on the intricate links between ferroptosis and disease pathogenesis, as well as the identification of potential targets for clinical treatment. Graphical Abstract. Ferroptosis, characterized by iron accumulation and lipid peroxidation, is emerging as a key player in various diseases, including cancers and neurological disorders. This review explores its involvement in spinal cord injuries and intervertebral disc degeneration, highlighting the need for further research to understand its role in disease pathogenesis and identify potential therapeutic targets.

PNS injury initiates transcriptional changes in Schwann cells, satellite glial cells and PNS neurons that facilitate regeneration. The signaling pathways that control these transcriptional changes are not fully understood. The canonical/β-catenin Wnt signaling pathway is active during early stages of PNS development, where it controls radial axonal sorting and the onset of PNS myelination. Upon PNS injury, the canonical Wnt signaling pathway is re-activated, suggesting that canonical Wnt signaling plays an important role in PNS regeneration. To explore the potential of the canonical Wnt signaling pathway as a therapeutic target in enhancement of PNS recovery, we used a combination of genetic and pharmacological approaches to either activate or inhibit canonical Wnt signaling during PNS recovery. We found that manipulating canonical Wnt signaling does not alter PNS regeneration. Our data suggest that the canonical Wnt signaling pathway is not a strong therapeutic target for the enhancement of PNS regeneration.

Magnetic resonance imaging (MRI) is central to noninvasive brain tumor assessment, yet clinical uptake of artificial intelligence depends on both accuracy and transparency. This study presents a lightweight and interpretable hybrid framework that fuses features from two efficient convolutional backbones, MobileNetV2 and EfficientNetV2B0, using late fusion with global average pooling and vector concatenation. Classification is performed with a K‑Nearest Neighbors (KNN) head configured with k = 5, Euclidean distance, and distance‑based weighting. The dataset contains 7,023 MRI images drawn from Figshare, SARTAJ, and BR35H. Data were split with a 20% held‑out test set and a validation set equal to 20% of the remaining training pool, yielding 64%/16%/20% train/val/test. Four diagnostic categories were evaluated: Glioma, Meningioma, Pituitary, and Notumor. The confusion matrix shows a compact diagonal, and class‑wise precision, recall, and F1 are consistently high on the test set. A 5‑fold cross‑validation with normality assessment and paired significance testing supports robustness across folds. On the held‑out test set, class‑wise ROC-AUC was 1.00 for all four classes, and overall accuracy was 99.69%. Results should be interpreted in light of the unified dataset; external validation is warranted. Clinical interpretability is supported by class‑wise Grad‑CAM overlays and SHAP analyses, including waterfall plots that quantify individual feature contributions. These findings indicate that a dual‑backbone late‑fusion design coupled with a simple nonparametric classifier delivers strong, balanced performance while providing anatomically plausible case‑level insight into model decisions.

An association between gastroesophageal reflux disease (GERD) and sleep disorder has been reported. However, the magnitude of this association remains poorly understood. Therefore, we aimed to systematically evaluate this relationship. We conducted a comprehensive search for observational studies in eight databases from their inception to February 28, 2025. The characteristics of each study and pooled risk ratio (RR) with corresponding confidence intervals were calculated. Subgroup analyses were performed to explore sources of heterogeneity. A total of eighteen studies involving 110,417 participants met the inclusion criteria and were included in this meta-analysis. Our findings indicate a statistically significant unidirectional association between GERD and sleep disorder (RR = 2.02, 95% CI 1.71 to 2.37). Subgroup analyses consistently demonstrated an association between sleep disorder and GERD regardless of the diagnostic tools used for either condition (P = 0.32 for GERD diagnosis tools and P = 0.80 for sleep disorder diagnosis tools). Sensitivity analysis indicates that the conclusions are highly stable, and GRADEpro evaluation results have a low level of evidence. This meta-analysis reveals a significant correlation between sleep disorder and GERD. More studies under consistent conditions are needed to validate these findings.