Increase of blood brain barrier (BBB) permeability after acute ischemia stroke is a predictor to intracerebral hemorrhage transformation (HT) for tissue plasminogen activator (tPA) thrombolysis and post-endovascular treatment. Previous studies showed that 2-h ischemia induced damage of BBB integrity and matrix metalloproteinase-2 (MMP-2) made major contribution to this disruption. A recent study showed that blocking β2-adrenergic receptor (β2-AR) alleviated ischemia-induced BBB injury by reducing hypoxia-inducible factor-1 alpha (HIF-1α) level. In this study, we sought to investigate the interaction of HIF-1α with MMP-2 and vascular endothelial growth factor (VEGF) in BBB injury after acute ischemia stroke. Rat suture middle cerebral artery occlusion (MCAO) model was used to mimic ischemia condition. Our results showed that ischemia produced BBB damage and MMP-2/9 upregulation was colocalized with Rhodamine-dextran leakage. Pretreatment with YC-1, a HIF-1α inhibitor, alleviated 2-h ischemia-induced BBB injury significantly accompanied by decrease of MMP-2 upregulation. In addition, YC-1 also prevented VEGF-induced BBB damage. Of note, VEGF was shown to be colocalized with neurons but not astrocytes. Taken together, BBB damage was reduced by inhibition of interaction of HIF-1α with MMP-2 and VEGF during acute cerebral ischemia. These findings provide mechanisms underlying BBB damage after acute ischemia stroke and may help reduce thrombolysis- and post-endovascular treatment-related cerebral hemorrhage.

Resting-state functional magnetic resonance imaging (R-fMRI) signals are spatiotemporally organized. R-fMRI studies in patients with classic trigeminal neuralgia (CTN) have suggested alterations in functional connectivity. However, far less attention has been given to investigations of the local oscillations and their frequency-specific changes in these patients. The objective of this study was to address this issue in patients with CTN. R-fMRI data from 17 patients with CTN and 19 age- and gender-matched healthy controls (HCs) were analyzed using amplitude of low-frequency fluctuation (ALFF). The ALFF was computed across different frequencies (slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz) in patients with CTN compared to HCs. In the typical band, patients with CTN showed increases of ALFF in bilateral temporal, occipital, and left middle frontal regions and in the left middle cingulate gyrus, as well as decreases of ALFF in the right inferior temporal region and in regions (medial prefrontal regions) of default mode network. These significant group differences were identified in different sub-bands, with greater brainstem findings in higher frequencies (slow-4) and extensive default mode network and right postparietal results in lower frequencies (slow-5). Furthermore, significant relationships were found between subjective pain ratings and both amplitudes of higher frequency (slow-4) blood oxygen level-dependent (BOLD) signals in pain localization brain regions and lower frequencies (slow-5) in pain signaling/modulating brain regions in the patients, and decreased ALFF within the prefrontal regions was significantly correlated with pain duration in the patients. This result supports our hypothesis that trigeminal pain has a characteristic spatiotemporal distribution of low-frequency BOLD signals. These findings might contribute to a better understanding of the impact of CTN on the brain’s intrinsic architecture. Future studies should take the frequencies into account when measuring brain resting BOLD signals of patients with CTN.

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Background: The prognosis of patients with osteosarcoma is still poor due to the lack of effective prognostic markers. The EMT (epithelial–mesenchymal transition) serves as a promoter in the progression of osteosarcoma. This study systematically analyzed EMT-related genes to explore new markers for predicting the prognosis of osteosarcoma. Methods: RNA-Seq data and clinical information were obtained from the GEO database; GSVA and GSEA analysis were used to enrich pathways related to osteosarcoma progression; LASSO method analysis was used to construct the prognosis risk signature. The “Nomogram” package generated the risk prediction nomogram, and its clinical applicability was evaluated by decision curve analysis (DCA). Results: GSVA and GSEA analysis showed that the EMT signaling pathway was closely related to osteosarcoma progression. A 9-genes signature (LAMA3, LGALS1, SGCG, VEGFA, WNT5A, MATN3, ANPEP, FUCA1, and FLNA) was constructed. The overall survival (OS) of the high-risk scores group was significantly lower than the low-risk scores group. The 9-gene signature demonstrated good predictive accuracy. Cox regression analysis showed that the 9-gene signature provided independent prognostic factors for osteosarcoma patients. In addition, the predictive nomogram model could effectively predict the prognosis of osteosarcoma patients. Conclusion: This study constructed a 9-gene signature as a new prognostic marker to predict osteosarcoma patients’ survival.

Dl-3-n-butylphthalide (dl-NBP) was approved by the FDA of China for the treatment of acute ischemic stroke. Dl-NBP has been shown to promote neurological functional recovery and enhance white matter integrity using an endothelin-1-induced focal permanent cerebral ischemia model, which could mimic those patients who have no opportunity to receive either tissue plasminogen activator (tPA) thrombolysis or endovascular therapy. However, it is not clear whether dl-NBP could promote neurological functional recovery in a focal transient cerebral ischemia model, which could mimic those patients who have the opportunity to receive either tPA thrombolysis or endovascular therapy. In this study, using a model of middle cerebral artery occlusion in mice, we aim to explore the effect of two-week dl-NBP treatment on neurological functional recovery after ischemic stroke as well as its underlying mechanism. Our results showed that dl-NBP treatment promoted functional recovery assessed by neurological scores and an adhesive remove test, and this improved the integrity of white matter after 60-min ischemia and 14-day reperfusion. In addition, dl-NBP increased the number of RECA-1 positive vessels and enhanced the expression of the tight junction protein occludin. More importantly, dl-NBP also promoted the expression of hypoxiainduced factor-1a, the vascular endothelial growth factor, Notch, and delta-like ligand 4. In conclusion, our study provides evidence that dl-NBP treatment could also promote functional recovery after focal transient ischemia stroke, and this recovery is associated with upregulated white matter integrity, microvessels, and the tight junction protein occludin. Our results suggested that, in future, dl-NBP may also be applied in clinic to promote functional recovery during the later phase of focal transient ischemic stroke.