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Cerebrovascular disease is a common chronic disease in the middle-aged and elderly population, with severe damage. Timely restoration of ischemia (ie blood reperfusion) in brain tissue can attenuate brain damage. The experiment investigated that the effects of USP38 in cerebral ischemia–reperfusion injury (CI–RI) and its possible mechanism. USP38 expression were down-regulated in patients with CI–RI model or mice with CI–RI model. USP38 alleviates neuroinflammation in vitro model of CI–RI model or mice model of CI–RI model by the activation of KDM5B. USP38 protein was interlinkaged with KDM5B protein in vitro model of CI–RI model. The regulation of KDM5B regulated the effects of USP38 in vitro model of CI–RI model. Our data demonstrated that USP38 protein alleviates neuroinflammation of cerebral ischemia–reperfusion injury via KDM5B expression, as a novel therapy to counteract inflammation of CI–RI.

BACKGROUND Ischemia-reperfusion injury is caused by a blood reperfusion injury in ischemic brain tissue, and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. MiR-122 is closely related to ischemia-reperfusion injury in the myocardium, kidney, and liver; however, the role in cerebral ischemia-reperfusion injury has not been established. MATERIAL AND METHODS In this study, cerebral ischemia-reperfusion injury was established in a rat model, and the control group was a sham-operated group. After ischemia-reperfusion injury for 6, 12, and 24 hours, brain tissue specimens were collected and the expression of miR-122 and DJ-1 were determined using quantitative real-time polymerase chain reaction. Flow cytometry was used to determine the reactive oxygen species (ROS) content. The modified Neurological Severity Score (mNSS) scale was used to evaluate the sensory and motor function defects of the rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and enzyme activity were determined. The rats in the cerebral ischemia-reperfusion injury model were divided into 2 groups (antagomir-NC group and antagomir miR-122 group). Brain neuron RN-c cells were divided into the following 4 groups: antagomir-NC, antagomir miR-122, pIRES2-blank, and pIRES2-DJ-1. Seventy-two hours after transfection, ischemia-reperfusion treatment was carried out and conventional cultured RN-c cells were used as the control group. Flow cytometry was used to detect apoptosis and western blot was used to detect the expression of DJ-1, PTEN, AKT, and p-AKT. RESULTS The expression of miR-122 increased significantly in the process of ischemia-reperfusion damage after cerebral infarction, while the expression of DJ-1 decreased significantly. Downregulation of miR-122 significantly increased the expression of DJ-1, enhanced the activity of the PTEN/PI3K/AKT pathway, reduced cell apoptosis, and alleviated cerebral ischemia-reperfusion injury. CONCLUSIONS Inhibition of miR-122 can decrease cerebral ischemia-reperfusion injury by upregulating DJ-1-PTEN/PI3K/AKT pathway.

Many studies have reported the recovery ability of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for neural diseases. In this study, the authors explored the roles of UC-MSCs to treat the traumatic brain injury. Umbilical cord-derived mesenchymal stem cells were isolated from healthy neonatal rat umbilical cord immediately after delivery. The traumatic brain injury (TBI) model was formed by the classical gravity method. The authors detected the behavior changes and measured the levels of inflammatory factors, such as interleukin-lβ and tumor necrosis factor-α by enzyme linked immunosorbent assay (ELISA) at 1, 2, 3, 4 weeks after transplantation between TBI treated and untreated with UC-MSCs. Simultaneously, the expression of glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) were measured by real-time–polymerase chain reaction and ELISA. The authors found that the group of transplantation UC-MSCs has a significant improvement than other group treated by phosphate buffered saline. In the behavioral test, the Neurological Severity Scores of UC-MSCs + TBI group were lower than TBI group (P

The purpose of this research is to explore the relationship between finance pressure and energy intensity using a firm-level data of Chinese manufacturing sectors. We introduce environmental regulation to our model to identify the technological channel through which finance pressure influence energy intensity. Our findings show that mitigation of finance pressure makes significant contribution to the reduction of energy intensity. As for the technological channel, environmental regulation plays a key role in pushing firms to invest in energy-efficiency technologies when funds are available. On the contrary, absence of environmental regulation would lead to investment in technologies that increase energy intensity. These finding are robust to different proxies for finance pressure and technology investment. Moreover, there are heterogeneous effects across regions and firms. In particular, firms in the eastern provinces and firms of non-foreign ownership are more likely to invest in energy-efficiency technologies when facing environmental regulation. These findings suggest financial policies and measures coordinate with environment and energy policies to make technological progress energy-efficiency oriented.

Alzheimer's disease (AD) is a progressive neurodegenerative disease which is characterized by the accumulation of amyloid-β peptide (Aβ). Orexin-A is a neuropeptide which has been reported to participate in the pathogenesis of AD. Thus, we aimed to investigate the possible mechanism by which Orexin-A acts in AD. APP/PS1 transgenic mice, an animal model of AD, were intracerebroventricularly injected with Orexin-A. Aβ-treated SH-SY5Y cells were used as a cell model of AD and treated with Orexin-A. The Morris water maze test, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA), electron microscopy, real-time PCR, and other biochemical assays were conducted. The Morris water maze test showed that Orexin-A aggravated cognitive deficit in APP/PS1 mice. Using thioflavine-S staining and ELISA, we found that Orexin-A promoted Aβ accumulation in APP/PS1 mice. By evaluating mitochondrial morphology, cytochrome c oxidase activity, ATP level, mitochondrial DNA copy number, and reactive oxygen species, we found that Orexin-A aggravated mitochondrial impairment in APP/PS1 mice and Aβ-treated SH-SY5Y cells. Our results indicate that Orexin-A exacerbates AD by inducing mitochondrial impairment. This is a new mechanism that explains how Orexin-A participates in the pathogenesis of AD.

Adult hippocampal neurogenesis occurs in the dentate gyrus (DG) of the mouse hippocampus, and plays roles in learning and memory progresses. In amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice, a rodent model of Alzheimer's disease (AD), severe impairment of neurogenesis in the dentate subgranular zone (SGZ) of the DG has been reported. Osthole, an active constituent of Cnidium monnieri (L.) CUSSON, has been reported to exert neuroprotective effects and may promote neural stem cell proliferation. However, whether osthole ameliorates spatial memory deficits and improves hippocampal neurogenesis in APP/PS1 mice remains unknown. In this study we found that osthole (30 mg/kg intraperitoneally (i.p.) once daily) treatment dramatically ameliorated the cognitive impairments by Morris Water Maze test and passive avoidance test, and augmented neurogenesis in the DG of hippocampus in APP/PS1 mice. Furthermore, osthole treatment upregulated expression of brain-derived neurotrophic factor (BDNF) and enhanced activation of the BDNF receptor tyrosine receptor kinase B (TrkB) following increased phosphorylation of cyclic AMP response element-binding protein (CREB), indicating that osthole improves neurogenesis via stimulating BDNF/TrkB/CREB signaling in APP/PS1 transgenic mice.

Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by a loss of projecting dopaminergic neurons in the substantia nigra and diminished dopamine level in the striatum. Dopaminergic deficit consequently leads to the alterations of striatal basal glutamatergic synaptic transmission and plasticity in the medium spiny neurons. The cytokines and neurotoxins released from the reactive immune cells induced the loss of the projecting dopaminergic neurons in the substantia nigra, which triggering the pathogenesis of PD. The present study investigated the effect of treatment with baicalein (5,6,7-trihydroxyflavone) on the central cytokine synthesis, striatal glutamatergic transmission, and behavioral performance in the rotarod task in the mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with baicalein significantly attenuated the upregulation of striatal basal glutamatergic strength by decreasing the presynaptic glutamate release and recovering the insertion of postsynaptic glutamate receptor subunit GluR1 induced by MPTP. It also significantly improved the behavioral performance in the rotarod task in the mice injected with MPTP. Treatment with baicalein decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1β) in the substantia nigra and striatum in the mice injected with MPTP. These results indicated that baicalein might serve as novel approach for the treatment of the patients with PD.

Purpose: We studied the association between admission white blood cell (WBC) count and short term outcome in patients with acute cerebral infarction. Methods: 2808 patients with acute cerebral infarction were included in the study. WBC count and other variables were collected within the first 24 hours of admission. Clinical outcomes (death or dependency) were evaluated by neurologists during hospitalization. The associations between WBC count and in-hospital death or dependency at discharge were analyzed using a multiple logistic model. Result: Multivariate-adjusted odds ratio (95% confidence intervals) of dependency associated with patients with WBC of 10.0-10.9×109/L, 11.0-11.9×109/L, ≥12.0×109/L were 1.46(0. 87-2. 45), 6.21(3. 70-10. 42) and 7.01(4. 53-10. 87), respectively, when compared with patients with admission WBC counts < 10.0x109/L. Multivariate-adjusted odds ratio (95% confidence intervals) of death associated with WBC 10.0-10.9×109/L, 11.0-11.9×109/L and ≥12.0×109/L were 2.098(0. 96-4. 58), 4.79(2. 24-10. 22) and 5.59(3. 14-9. 98), respectively. Conclusion: Increased WBC count at admission was significantly and positively associated with in-hospital death or dependency at discharge among patients with acute cerebral infarction.