44 research outputs found
Transfusion of Resting Platelets Reduces Brain Hemorrhage After Intracerebral Hemorrhage and tPA-Induced Hemorrhage After Cerebral Ischemia
BackgroundExacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation.MethodsMice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 h of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 min. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 h.ResultsPlatelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia.ConclusionOur findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke
Growth Differentiation Factor 11 Promotes Neurovascular Recovery After Stroke in Mice
Background: Growth differentiation factor 11 (GDF11), a member of transforming growth factor-β (TGF-β) superfamily, was shown to rejuvenate cardiac and skeletal muscle function and to improve cerebral vasculature and neurogenesis in old mice. However, recent experimental data reported that raising GDF11 levels inhibited skeletal muscle regeneration and had no effect on cardiac hypertrophy. Our aim was to investigate the effects of GDF11 on brain repair during the recovery phase after stroke.Methods: Mice were subjected to distal middle cerebral artery occlusion, and recombinant GDF11 (rGDF11) was injected intraperitoneally once a day during days 7–13 after stroke. Neuronal precursor cells (NPCs) proliferation and angiogenesis were assayed at 14 days. Neuronal regeneration was assayed at 42 days. The beam-walking test and CatWalk were used to evaluate behavioral functions. Downstream pathways of GDF11 were also investigated.Results: GDF11 was upregulated in the ipsilateral peri-infarct cortex and subventricular zone (SVZ) at 14 days after stroke. Treatment with rGDF11 enhanced the number of newborn NPCs and endothelial cells, microvascular length and area, and brain capillary perfusion. Western blots showed that rGDF11 upregulated brain-derived neurotrophic factor (BDNF) and increased the levels of proangiogenic factor angiopoietin-2 (Ang-2) and phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2). We also found that rGDF11 upregulated the transcription factors Smad2 and Smad3 phosphorylation, but these activations were blocked by a TGF-β receptor inhibitor SB431542. Moreover, rGDF11-induced angiogenic remodeling and NPCs proliferation were reversed by injection of SB431542, suggesting that GDF11 may exert its effect via the TGF-β/Smad2/3 signaling pathway. Finally, treating mice with rGDF11 resulted in a significant increase in neuronal regeneration and functional recovery.Conclusion: GDF11 promoted neurogenesis and angiogenesis and contributed to functional recovery after stroke in mice
Validation and Analysis of <i>COIL</i>, a Gene Associated with Multiple Lambing Traits in Sheep
In a past study, the team used specific-locus amplified fragment sequencing (SLAF sequencing) to detect single-nucleotide polymorphisms (SNPs) contributing to the differences in lambing numbers in Xinjiang sheep. This study verified the correlation between the COIL gene and lambing number characters in sheep and explored its possible mechanism of action. In this study, three SNPs in the COIL gene, namely COILSNP1 (rs7321466), COILSNP2 (rs7314134), and COILSNP3 (rs7321563), were explored in terms of their possible mechanism of action. A tissue expression profiling analysis revealed that the COIL gene was significantly more expressed in the uterus and ovaries than in other tissues (p p COIL gene significantly increased the proliferation of mouse ovarian fibroblasts and sheep fibroblasts (p COIL gene significantly increased the activity of sheep fibroblasts (p p COIL gene affected the biogenesis pathway of spliceosomal U snRNPs by validating protein network connections. This activity affects ovulation, embryonic development, and changes in lambing size in sheep
Effect of swelling clay dispersion type on fine coal flotation
The influence of bentonite dispersion on fine coal flotation was examined to better understand the role of swelling clay in the process of flotation. It was found that the coal flotation recovery was lower with uncontrolled dispersion of bentonite than with controlled dispersion. The detrimental effect was attributed to the increase in slime coating. In the uncontrolled dispersion, the dispersed bentonite platelets formed an extensive card-house structure. The three-dimensional networks increased the slurry viscosity, and caused significant coating of the coal particles, thereby inhibiting particle mobility and bubble-particle attachment. In the controlled dispersion, the bentonite mineral appeared as separate particles with low aspect ratios. The coal particles were partially coated, and the slurry viscosity was lower, resulting in higher flotation recovery. The findings in this study suggested that a practical solution to mitigate the negative impact of swelling clay on flotation would be to maintain high electrolyte levels in the wash water to inhibit clay swelling and dispersion
The Complete Mitochondrial Genome of the Damsel Bug Alloeorhynchus bakeri (Hemiptera: Nabidae)
<p>The complete sequence of the mitochondrial DNA (mtDNA) of the damsel bug, <i>Alloeorhynchus bakeri</i>, has been completed and annotated in this study. It represents the first sequenced mitochondrial genome of heteropteran family Nabidae. The circular genome is 15, 851 bp in length with an A+T content of 73.5%, contains the typical 37 genes that are arranged in the same order as that of the putative ancestor of hexapods. Nucleotide composition and codon usage are similar to other known heteropteran mitochondrial genomes. All protein-coding genes (PCGs) use standard initiation codons (methionine and isoleucine), except<i> COI</i>, which started with TTG. Canonical TAA and TAG termination codons are found in eight protein-coding genes, the remaining five (<i>COI</i>, <i>COII</i>, <i>COIII</i>, <i>ND5</i>, <i>ND1</i>) have incomplete termination codons (T or TA). PCGs of two strands present opposite CG skew which is also reflected by the nucleotide composition and codon usage. All tRNAs have the typical clover-leaf structure, except the dihydrouridine (DHU) arm of<i> tRNA<sup>Ser (AGN)</sup> </i>which forms a simple loop as known in many other metazoa. Secondary structure models of the ribosomal RNA genes of <i>A. bakeri</i> are presented, similar to those proposed for other insect orders. There are six domains and 45 helices and three domains and 27 helices in the secondary structures of<i> rrnL</i> and <i>rrnS</i>, respectively. The major non-coding region (also called control region) between the small ribosomal subunit and the <i>tRNA<sup>Ile </sup></i>gene includes two special regions. The first region includes four 133 bp tandem repeat units plus a partial copy of the repeat (28 bp of the beginning), and the second region at the end of control region contains 4 potential stem-loop structures. Finally, PCGs sequences were used to perform a phylogenetic study. Both maximum likelihood and Bayesian inference analyses highly support Nabidae as the sister group to Anthocoridae and Miridae.</p