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Background: miR-126-5p plays an important role in promoting endothelial cell (EC) proliferation. We thus explored whether miR-126-5p can promote EC proliferation and angiogenesis in chronically ischemic brains (CIBs). Results: Improved revascularization in moyamoya patients was correlated with upregulated miR-126-5p expression in the TM and DM. In vitro experiments showed that miR-126-5p promoted EC proliferation through the PI3K/Akt pathway. CIBs from the agomir group exhibited significantly higher p-Akt, VEGF, CD31 and eNOS expression compared with the control CIBs. The ICBP and the RCF were significantly better in the agomir compared with the control group. Conclusion: Increasing miR-126-5p expression in the TM can promote EC proliferation and angiogenesis in CIBs of 2VO+EMS rats through the PI3K/Akt pathway. Methods: We assessed the correlation between revascularization and miR-126-5p expression in the temporal muscle (TM) and dura mater (DM) of moyamoya patients. The effect of miR-126-5p on EC proliferation and downstream signaling pathways was explored in vitro. We established an animal model of two-vessel occlusion plus encephalo-myo-synangiosis (2VO+EMS), transfected the TM with miR-126-5p agomir/antagomir, compared the expression of miR-126-5p and relevant downstream cytokines in brain tissue among different groups, and investigated the improvement in cerebral blood perfusion (ICBP) and the recovery of cognitive function (RCF).

Background and Aims: It has recently emerged the concept of “obesity paradox,” a term used to describe an inverse association between obesity and clinical outcomes in cardiovascular diseases and stroke. The purpose of this study was to investigate the association between body mass index (BMI) and the risk of intracranial aneurysm rupture.Methods: In this study, we conducted a retrospective analysis of a prospectively maintained database of patients with intracranial aneurysms from 21 medical centers in China. A total of 3,965 patients with 4,632 saccular intracranial aneurysms were enrolled. Patients were separated into unruptured (n = 1,977) and ruptured groups (n = 1,988). Univariable and multivariable logistic regression analyses were performed to determine the association between BMI and intracranial aneurysm rupture.Results: Compared to the patients with normal BMI (18.5 to < 24.0 kg/m2), the odds of intracranial aneurysm rupture were significantly lower in patients with BMI 24.0 to < 28.0 kg/m2 (OR = 0.745, 95% CI = 0.638–0.868, P = 0.000) and patients with BMI ≥ 28.0 kg/m2 (OR = 0.628, 95% CI = 0.443–0.890, P = 0.009). Low BMI (<18.0 kg/m2) was not associated with intracranial aneurysm rupture (OR = 0.894, 95% CI = 0.483–1.657, P = 0.505). For males, both the BMI 24.0 to < 28.0 kg/m2 (OR = 0.606, 95% CI = 0.469–0.784, P = 0.000) and the BMI ≥ 28.0 kg/m2 (OR = 0.384, 95% CI = 0.224–0.658, P = 0.001) were associated with a lower rupture risk, whereas the inverse association was not observed in females. Both the BMI 24.0 to < 28.0 kg/m2 (OR = 0.722 for aged 50–60y, 95% CI = 0.554–0.938, P = 0.015; OR = 0.737 for aged >60y, 95% CI = 0.586–0.928, P = 0.009) and the BMI ≥ 28.0 kg/m2 (OR = 0.517 for aged 50–60y, 95% CI = 0.281–0.950, P = 0.0034; OR = 0.535 for aged >60y, 95% CI = 0.318–0.899, P = 0.0018) was associated with a lower rupture risk in patients aged ≥50 years, whereas the association was not significant in patients aged <50 years.Conclusions: Increased BMI is significantly and inversely associated with saccular intracranial aneurysm rupture in males and patients aged ≥50 years.

Traumatic brain injury (TBI) is considered as the most common cause of disability and death, and therefore an effective intervention of cascade pathology of secondary brain injury promptly can be a potential therapeutic direction for TBI prognosis. Further study of the physiological mechanism of TBI is urgent and important. Phosphoglycerate mutase 5 (Pgam5), a mitochondrial protein, mediate mitochondrial homeostasis, cellular senescence, and necroptosis. This study evaluated the effects of Pgam5 on neurological deficits and neuroinflammation of controlled cortical impact-induced TBI mouse model in vivo and LPS + ATP-induced microglia model in vitro. Pgam5 was overexpressed post-TBI. Pgam5 depletion reduced pyroptosis-related molecules and improved microglia activation, neuron damage, tissue lesion, and neurological dysfunctions in TBI mice. RNA-seq analysis and molecular biology experiments demonstrated that Pgam5 might regulate inflammatory responses by affecting the post-translational modification and protein expression of related genes, including Nlrp3, caspase1, Gsdmd, and Il-1β. In microglia, Pgam5-sh abrogated LPS + ATP-induced Il-1β secretion through Asc oligomerization-mediated caspase-1 activation, which was independent of Rip3. The data demonstrate the critical role Pgam5 plays in nerve injury in the progression of TBI, which regulates Asc polymerization and subsequently caspase1 activation, and thus reveals a fundamental mechanism linking microglial inflammasome activation to Asc/caspase1-generated Il-1β-mediated neuroinflammation. Thus, our data indicate Pgam5 worsens physiological and neurological outcomes post-TBI, which may be a potential therapeutic target to improve neuroinflammation after TBI.

Glioblastoma (GBM) patients present poor prognosis. Deubiquitination by deubiquitinating enzymes (DUBs) is a critical process in cancer progression. Ubiquitin-specific proteases (USPs) constitute the largest sub-family of DUBs. Evaluate the role of USP32 in GBM progression and provide a potential target for GBM treatment. Clinical significance of USP32 was investigated using Gene Expression Omnibus databases. Effects of USP32 on cell growth and metastasis were studied in vitro and in vivo. Differentially expressive genes between USP32-knockdown U-87 MG cells and negative control cells were detected using RNA sequencing and used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomic pathway enrichment analyses. Finally, RT-qPCR was used to validate the divergent expression of genes involved in the enriched pathways. USP32 was upregulated in GBM patients, being correlated to poor prognosis. USP32 downregulation inhibited cell growth and metastasis in vitro. Furthermore, USP32 knockdown inhibited tumorigenesis in vivo. In addition, UPS32 was identified as a crucial regulator in different pathways including cell cycle, cellular senescence, DNA replication, base excision repair, and mismatch repair pathways. USP32 acts as an oncogene in GBM through regulating several biological processes/pathways. It could be a potential target for GBM treatment.