Huatanmaitong tablet alleviate cerebral ischemic reperfusion injury with hyperlipidaemia in rats by regulating OATPs/VEGF axis.

Stroke is the top priority pathogenesis of disability and death globally, affecting people worldwide. The presence of high levels of lipids in the blood has been confirmed as a vital factor of ischemic stroke. We aim to examine the effectiveness of Huatanmaitong tablet in hyperlipidemia rats that have experienced an ischemic stroke. We created a rat model of middle cerebral artery occlusion (MCAO) with hyperlipidemia as a basis. Following 8 weeks of high-fat diet, the model rats underwent MCAO surgery. Subsequently, the rats were administered huatanmaitong tablets and lipitor tablets as treatments. Therefore there are five groups, CONTROL, MCAO, hyperlipidemia (HLP), Huatanmaitong tablet (HTMTT) and Lipitor (LIPITOR) groups respective ly. To assess the efficacy of the medication, the serum lipid levels of rats were measured both prior to and following administration. Hematoxylin eosin staining was used to observe the alterations in the brain and liver structures within each group. VEGF and OATPs related factors were detected in brain, liver by using immunohistochemistry, Western blotting, and Quantitative PCR. After the model was established successfully, the infarct volume and behavioral scores of the model group, hyperlipidemia group, Huatan Maitong tablet group and Lipitor group had statistical differences (P<0.05). Blood lipid levels of rats were measured before and after treatment, and it was found that Huatanmaitong tablets effectively reduced these levels. Hematoxylin and eosin staining of the brain and liver showed that huatanmaitong tablets maintained the microstructure stability. Western blotting and real-time PCR revealed that Huatanmaitong tablets improved the expression level of organic anion transport (OATP1B1, OATP2B1) in rat tissues with ischemic stroke, enhancing the transmembrane transport of exogenous substances and maintaining homeostatic balance. Additionally, it down-regulated the expression of VEGF in various organs such as the brain, and liver, demonstrating the ability of Huatanmaitong tablets to remove phlegm, blood stasis, and promote circulation by regulating serum lipid levels, organic anion transport peptide, and VEGF in rats. The behavioral score of ischemic stroke rats can be improved and the neurological impairment symptoms of rats can be alleviated by Huatanmaitong tablet through the regulation of OATPS/VEGF axis.

Geniposide attenuates early brain injury by inhibiting oxidative stress and neurocyte apoptosis after subarachnoid hemorrhage in rats.

BACKGROUND: Oxidative stress and neurocyte apoptosis are crucial pathophysiological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Geniposide (GNP) has been reported to exert neuroprotective effects by reducing oxidative injury and neurocyte apoptosis. However, the effect of GNP has not been clarified in EBI after SAH. The study was performed to evaluate the neuroprotective effects and mechanisms of GNP in EBI after SAH. METHODS AND RESULTS: A total of 60 male Wistar rats were randomly divided into five groups. The prechiasmatic cistern SAH model was used in this study. SAH grade was evaluated using a grading system. Neurological function was evaluated using the Garcia scores. Brain edema was measured by the wet-dry method. Blood-brain barrier (BBB) permeability was measured by the extravasation of Evans Blue (EB). The neurocyte apoptosis was observed using TUNEL assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and quinone oxidoreductase-1 (NQO-1) were performed. The results showed that GNP reduced brain edema, attenuated BBB permeability, inhibited neurocyte apoptosis and improved neurological function. Moreover, GNP also decreased the levels of ROS and MDA, elevated Nrf2 expression in the temporal cortex and up-regulated the expression of NQO-1, HO-1 and GST after SAH. CONCLUSIONS: GNP could ameliorate oxidative stress and neurocyte apoptosis to exert neuroprotective effects by Nrf2 pathway.

Vertically aligned CNT-Cu nano-composite material for stacked through-silicon-via interconnects.

For future miniaturization of electronic systems using 3D chip stacking, new fine-pitch materials for through-silicon-via (TSV) applications are likely required. In this paper, we propose a novel carbon nanotube (CNT)/copper nanocomposite material consisting of high aspect ratio, vertically aligned CNT bundles coated with copper. These bundles, consisting of hundreds of tiny CNTs, were uniformly coated by copper through electroplating, and aspect ratios as high as 300:1 were obtained. The resistivity of this nanomaterial was found to be as low as ∼10(-8) Ω m, which is of the same order of magnitude as the resistivity of copper, and its temperature coefficient was found to be only half of that of pure copper. The main advantage of the composite TSV nanomaterial is that its coefficient of thermal expansion (CTE) is similar to that of silicon, a key reliability factor. A finite element model was set up to demonstrate the reliability of this composite material and thermal cycle simulations predicted very promising results. In conclusion, this composite nanomaterial appears to be a very promising material for future 3D TSV applications offering both a low resistivity and a low CTE similar to that of silicon.

The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia-reperfusion injury via regulating NR2B-ERK/CREB signaling.

BACKGROUND AND PURPOSE: Cerebral ischemia-reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N-methyl-D-aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I/R injury. METHODS: We used in vivo and in vitro models of cerebral I/R injury for middle cerebral artery occlusion/reperfusion in mice and oxygen-glucose deprivation/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I/R injury, and whether the protective mechanism was related to the regulation of NMDAR-ERK/CREB signaling. RESULTS: Treatment with Ast+Lig, or MK-801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca2+ influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I/R injury based on 2,3,5-triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I/R injury based on western blotting and reverse transcription-quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I/R injury. CONCLUSIONS: The overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I/R injury via regulation of the NR2B-ERK/CREB signaling pathway.

Protective Effects of Astragalus Membranaceus and Ligustrazine on Rat Brain Microvascular Endothelial Cell Injury after Oxygen-Glucose Deprivation/ Reoxygenation by Suppressing the PKCδ/MARCKS Pathway.

AIM AND OBJECTIVE: Cell death is a main pathological change in brain ischemia. Astragalus membranaceus (Ast) and ligustrazine (Lig), as traditional Chinese herbs, have a protective effect against ischemia-reperfusion injury. We aim to find whether the underlying protective mechanism of Astragalus membranaceus and ligustrazine against Oxygen-glucose deprivation/reoxygenation (OGD/R) -induced injury in RBMECs is related to PKCδ/MARCKS pathway. MATERIALS AND METHODS: OGD/R preconditioning was instituted in rat brain microvascular endothelial cells (RBMECs). The survival and apoptosis of RBMECs were detected by a Cell Counting Kit-8 and TUNEL staining; PKCδ/MARCKS and MMP9 expression were examined by immunofluorescence, western blot and quantitative real-time PCR. RESULTS: OGD/R stimulation significantly increased RBMEC apoptosis, whereas Ast+Lig, Rottlerin or Ast+Lig+Rottlerin treatment evidently reduced cellular apoptosis and increased cell viability (P <0.05). Furthermore, Ast+Lig, Rottlerin or Ast+Lig+Rottlerin treatment significantly reduced mRNA expression levels of PKCδ/MARCKS and MMP9 (P <0.05), compared to OGD/R control group. Moreover, Ast+Lig, Rottlerin or Ast+Lig+Rottlerin treatment evidently reduced protein expression levels of PKCδ, MMP9, and MARCKS (P <0.05), compared to OGD/R control group, detected by western blotting or immunofluorescence. CONCLUSION: The administration of Astragalus membranaceus and ligustrazine protected RBMECs against OGD/R-induced apoptosis. PKCδ/MARCKS and MMP9 expression were significantly increased after OGD/R stimulation, while Astragalus membranaceus and ligustrazine treatment evidently suppressed. Collectively, Astragalus membranaceus and ligustrazine play protective effects against OGD/R-induced injury in RBMECs through regulating PKCδ/MARCKS pathway to inhibit MMP9 activation.

microRNA-421-3p prevents inflammatory response in cerebral ischemia/reperfusion injury through targeting m6A Reader YTHDF1 to inhibit p65 mRNA translation.

OBJECTIVE: Ischemic stroke is one of the leading causes of death globally, and inflammation is considered as a vital contributor to the pathophysiology of ischemic stroke. Recently, microRNA-421-3p-derived macrophages is found to promote motor function recovery in spinal cord injury. Here, we explored whether microRNA-421-3p is involved in inflammation responses during cerebral ischemia/reperfusion (I/R) injury and its molecular mechanism. METHODS: An in vivo experimental animal model of intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R) and in vitro model of microglial subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) were used. The effects of microRNA-421-3p on cerebral I/R injury and its underlying mechanism were detected by quantitative real-time PCR, western blotting, immunofluorescence staining, RNA immunoprecipitation, flow cytometry, luciferase reporter assay, and bioinformatics analysis. RESULTS: We find that microRNA-421-3p is significantly decreased in cerebral I/R injury in vitro and in vivo. Furthermore, overexpression of microRNA-421-3p evidently suppresses pro-inflammatory factor expressions and inhibits NF-κB p65 protein expression and nuclear translocation in BV2 microglia cells treated with OGD/R. However, microRNA-421-3p neither promotes p65 mRNA expression, nor affects p65 mRNA or protein stability. Moreover, we find the m6A 'reader' protein YTH domain family protein 1 (YTHDF1) is the specific target of microRNA-421-3p, and YTHDF1 specifically binds to the m6a site of p65 mRNA to promote its translation. CONCLUSION: microRNA-421-3p prevents inflammatory response in cerebral ischemia/reperfusion injury through targeting YTHDF1 to inhibit p65 mRNA translation. These findings provide novel insights into understanding the molecular pathogenesis of cerebral I/R injury.

Computer-assisted virtual operation planning in anterior controllable anterior-displacement and fusion surgery for ossification of the posterior longitudinal ligament based on actual computed tomography data.

OBJECTIVES: To investigate the effect of computer-assisted virtual operation planning (CAVOP) on anterior controllable anterior-displacement and fusion (ACAF) surgery for ossification of the posterior longitudinal ligament (OPLL). PATIENTS AND METHODS: A total of 25 patients with OPLL were enrolled in the study from September 2017 to December 2017. Preoperative Computed tomography (CT) scanning data were input into Mimics software to reconstruct three-dimensional (3D) models of actual cervical OPLL.Preoperative simulation of each surgical procedure and measurement of main parameters for intraoperative decision were conducted. Postoperative CT were used to test the clinical value of the preoperative planning. Width of vertebrae-OPLL complex (VOC), thickness of resected vertebral body (VB), height of intervertebral spacer, and length of screws and anterior plate were analyzed. RESULTS: There were no significant differences between the length of screws, width of VOC, and thickness of anterior resection of vertebrae in preoperative CT and postoperative CT. Statistical differences were found between preoperative and postoperative height of intervertebral space and length of anterior plate. CONCLUSION: A virtual ACAF surgical procedure for OPLL is feasible and useful clinically in surgical planning. It may provide a valuable tool for surgeons in formulating an appropriate surgical plan.

Curcumin mitigates cerebral vasospasm and early brain injury following subarachnoid hemorrhage via inhibiting cerebral inflammation.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and early brain injury is a fatal clinical syndrome. Cerebral vasospasm and early brain injury are associated with inflammatory response and oxidative stress. Whether curcumin, which plays important roles to regulate inflammatory cytokines and inhibit oxidative stress, inhibits SAH-induced inflammation and oxidative stress are largely unknown. METHODS: Adult male rats underwent autologous blood injection into prechiasmatic cistern to induce SAH. Curcumin (150 mg/kg) was administered at 0.5, 24 and 48 hr post-SAH. Mortality calculation and neurological outcomes as well as morphological vasospasm of anterior cerebral artery were studied. Superoxide dismutase, lipid peroxidation, and inflammatory cytokines (MCP-1 and TNF-α) expression in prefrontal region were quantified. Furthermore, p65 and phosphor-p65 were quantitatively analyzed. RESULTS: Curcumin remarkedly reduced mortality and ameliorated neurological deficits after SAH induction (p < .05); morphological results showed that cerebral vasospasm in curcumin-treated group was mitigated (p < .05). SAH-induced MCP-1 and TNF-α overexpression were inhibited in curcumin-treated group (p < .05). Importantly, phosphor-p65 was significantly inhibited after curcumin treatment (p < .05). CONCLUSIONS: Curcumin can inhibit SAH-induced inflammatory response via restricting NF-κB activation to alleviate cerebral vasospasm and early brain injury.

Control of Nanoplane Orientation in voBN for High Thermal Anisotropy in a Dielectric Thin Film: A New Solution for Thermal Hotspot Mitigation in Electronics.

High anisotropic thermal materials, which allow heat to dissipate in a preferential direction, are of interest as a prospective material for electronics as an effective thermal management solution for hot spots. However, due to their preferential heat propagation in the in-plane direction, the heat spreads laterally instead of vertically. This limitation makes these materials ineffective as the density of hot spots increases. Here, we produce a new dielectric thin film material at room temperature, named vertically ordered nanocrystalline h-BN (voBN). It is produced such that its preferential thermally conductive direction is aligned in the vertical axis, which facilitates direct thermal extraction, thereby addressing the increasing challenge of thermal crosstalk. The uniqueness of voBN comes from its h-BN nanocrystals where all their basal planes are aligned in the direction normal to the substrate plane. Using the 3ω method, we show that voBN exhibits high anisotropic thermal conductivity (TC) with a 16-fold difference between through-film TC and in-plane TC (respectively 4.26 and 0.26 W·m-1·K-1). Molecular dynamics simulations also concurred with the experimental data, showing that the origin of this anisotropic behavior is due to the nature of voBN's plane ordering. While the consistent vertical ordering provides an uninterrupted and preferred propagation path for phonons in the through-film direction, discontinuity in the lateral direction leads to a reduced in-plane TC. In addition, we also use COMSOL to simulate how the dielectric and thermal properties of voBN enable an increase in hot spot density up to 295% compared with SiO2, without any temperature increase.