Effects of adolescent alcohol exposure on oligodendrocyte lineage cells and myelination in mice: Age and subregion differences.

Adolescence is an important phase for the structural and functional development of the brain. The immaturity of adolescent brain development is associated with high susceptibility to exogenous disturbances, including alcohol. In this study, the acquisition of conditioned place preference (CPP) in adolescent mice by alcohol (2 g/kg) and the parvalbumin-positive interneurons (PV+ interneurons), oligodendrocyte lineage cells (OPCs), and myelination in the medial prefrontal cortex (mPFC) were assessed. We aim to determine the age- and subregional-specificity of the effects of alcohol. Alcohol (2 g/kg) was injected intraperitoneally on even days, and saline was injected intraperitoneally on odd days. The control group received a continuous intraperitoneal injection with saline. Differences in alcohol-induced CPP acquisition were assessed, followed by immunohistochemical staining. The results showed a pronounced CPP acquisition in 4- and 5-week-old mice. In the mPFC, there were reduced PV+ interneurons and OPCs in 3-week-old mice and reduced oligodendrocyte numbers in 4-week-old mice. The 5-week-old mice showed impaired myelination and a decrease in the number of PV+ interneurons, mature oligodendrocytes, and OPCs in the mPFC. Since the alterations in 5-week-old mice are more pronounced, we further explored the mPFC-associated subregional-specificity. In the alcohol-exposed mice, the oligodendrocyte numbers were decreased in the anterior cingulate cortex (ACC), PV+ interneuron numbers were declined in the prelimbic cortex (PL), and the number of oligodendrocytes, PV+ interneurons, and OPCs was also decreased with impaired myelination in the infralimbic cortex (IL). Our data suggest that adolescent alcohol exposure notably affected the acquisition of CPP, myelin formation, and the counts of PV+ interneurons, mature oligodendrocytes, and OPCs in the mPFC in 5-week-old mice. Also, the IL subregion was the worst-affected subregion of the mPFC in alcohol-exposed 5-week-old mice. It reveals that the effects of alcohol on adolescence and its mPFC myelination show obvious age- and subregional-specificity.

NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/ß-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of ß-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion: The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/ß-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Stellate ganglion block relieves acute lung injury induced by severe acute pancreatitis via the miR-155-5p/SOCS5/JAK2/STAT3 axis.

Acute lung injury (ALI), a prevalent complication of severe acute pancreatitis (SAP), is also a leading contributor to respiratory failure and even death of SAP patients. Here, we intended to investigate the function and mechanism of stellate ganglion block (SGB) in ameliorating SAP-induced ALI (SAP-ALI). We engineered an SAP-ALI model in rats and treated them with SGB. HE staining and the dry and wet method were implemented to evaluate pathological alterations in the tissues and pulmonary edema. The rats serum changes of the profiles of TNF-α, IL-6, IL-1ß, and IL-10 were examined. The profiles of miR-155-5p and SOCS5/JAK2/STAT3 were detected. Functional assays were performed for confirming the role of miR-155-5p in modulating the SOCS5/JAK2/STAT3 pathway in pulmonary epithelial cells. Our findings revealed that SGB vigorously alleviated SAP rat lung tissue damage and lung edema and lessened the generation of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. SGB enhanced SOCS5 expression, hampered miR-155-5p, and suppressed JAK2/STAT3 pathway activation. As evidenced by mechanism studies, miR-155-5p targeted the 3'UTR of SOCS5 and repressed its expression, hence resulting in JAK2/STAT3 pathway activation. During animal trials, we discovered that SGB ameliorated SAP-ALI, boosted SOCS5 expression, and mitigated the levels of pro-inflammatory factors and miR-155-5p in the plasma. In vitro, miR-155-5p overexpression substantially facilitated pulmonary epithelial cell apoptosis, inflammation, and JAK2/STAT3 pathway activation and restrained SOCS5 expression. All in all, our work hinted that SGB could modulate the miR-155-5p/SOCS5/JAK2/STAT3 axis to alleviate SAP-ALI.

Co-treatment with miR-21-5p inhibitor and Aurora kinase inhibitor reversine suppresses breast cancer progression by targeting sprouty RTK signaling antagonist 2.

Numerous studies have reported the regulatory effects of miR-21-5p and reversine in human breast cancer (HBC). However, the mechanism of reversine and miR-21-5p has not been fully investigated in HBC. The aim of the current study was to assess the mechanism of action of reversine, with or without miR-21-5p, in HBC progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot results confirmed the upregulation of miR-21-5p and downregulation of sprouty RTK signaling antagonist 2 (SPRY2) in HBC. Bioinformatics analysis and luciferase assay identified the correlation between miR-21-5p and SPRY2. Cell function experiment results indicated a decrease in migration, proliferation, and invasion of HBC cells treated with miR-21-5p inhibitor and reversine; however, an increase in apoptosis was observed in these cells. Apoptotic ability was more enhanced and migration, proliferation, and invasion were more impaired in HBC cells treated with both miR-21-5p inhibitor and reversine than in those treated individually with either inhibitors. SPRY2, downstream of miR-21-5p, participated in HBC progression with reversine. Overall, our study proved that combining the miR-21-5p inhibitor with reversine produced a synergistic effect by regulating SPRY2, thereby limiting HBC progression. This knowledge might offer insights into the clinical therapy of HBC.

Ultrasonic measurement of optic nerve sheath diameter in elderly patients with craniocerebral injury.

OBJECTIVE: To explore the application value of ultrasonic measurement of optic nerve sheath diameter in elderly patients with craniocerebral injury. METHODS: 86 cases of elderly patients with craniocerebral injury treated in our hospital between January 2017 and December 2018 were included, all of whom had the invasive monitoring of intracranial pressure (ICP) and optic nerve sheath diameter (ONSD) in ultrasonic testing. According to ICP measurement results, patients were divided into a normal ICP group (n = 44) and an increased ICP group (ICP ≥ 20 mmHg stood for increased ICP, n = 42). Gender, age, systolic blood pressure, blood glucose, hospital stay, oxyhemoglobin saturation, ISS score, ONSD value, hematoma type, primary injury, associated injury and complications of the patients were compared. RESULTS: The univariate analysis showed that the systolic blood pressure in the ICP increased group was significantly decreased while the blood glucose, ISS and ONSD values showed significant increase (P < 0.05). The multivariate analysis showed that associated injury, systolic blood pressure and ONSD value had a significant influence on the increase of intracranial pressure (all P < 0.05). ONSD is positively correlated with ICP (r = 0.855, P = 0.000). The areas of systolic blood pressure and ONSD value under the curve in diagnosis of increased intracranial pressure in elderly patients with craniocerebral injury were 0.717 and 0.780, respectively. When the ONSD value was 4.90 mm, the area under the curve was 0.780, the sensitivity and specificity were 89.00% and 91.00%, respectively. When the ONSD value predicted that the critical value of good/poor prognosis of patients was 4.70 mm, the area under the curve was 0.796, the sensitivity was 91.00%, and the specificity was 90.00%. CONCLUSION: Ultrasound measurement of optic nerve sheath diameter can diagnose the increase of intracranial pressure in elderly patients with craniocerebral injury, and can better predict the prognosis.