LncRNA-1810034E14Rik reduces microglia activation in experimental ischemic stroke.

BACKGROUND: Activation of microglial cells plays an important role in neuroinflammation after ischemic stroke. Inhibiting the activation of microglial cells has been suggested as a potential therapeutic approach in the treatment of ischemic stroke. METHODS: Oxygen-glucose deprivation in primary microglial cells and transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice were used as the in vitro and in vivo ischemic stroke models. Microarray analysis was performed to investigate the overall impact of long non-coding RNAs (lncRNAs) on the inflammation status of microglial cells. RT-qPCR was used to evaluate the lncRNA levels and mRNA levels of cytokines and microglial cell markers. ELISA was taken to measure the level of cytokines. Immunofluorescence was used to observe the activation of microglial cells. Western blotting was performed to test the p65 phosphorylation. RESULTS: In this study, we showed that LncRNA-1810034E14Rik was significantly decreased in LPS-treated or oxygen-glucose deprivation-induced microglial cells. Overexpression of 1810034E14Rik decreased the infarct volume and alleviated brain damage in MCAO mice. 1810034E14Rik overexpression reduced the expression of inflammatory cytokines not only in ischemic stroke mice but also in oxygen-glucose deprivation-induced microglial cells. Moreover, 1810034E14Rik overexpression could suppress the activation of microglial cells and inhibit the phosphorylation of p65. CONCLUSIONS: LncRNA-1810034E14Rik plays an anti-inflammatory role in ischemic stroke and regulates p65 phosphorylation, making it a potential target for stroke treatment.

Malibatol A regulates microglia M1/M2 polarization in experimental stroke in a PPARγ-dependent manner.

BACKGROUND: Activation of microglia plays a crucial role in immune and inflammatory processes after ischemic stroke. Microglia is reported with two opposing activated phenotypes, namely, classic phenotype (M1) and the alternative phenotype (M2). Inhibiting M1 while stimulating M2 has been suggested as a potential therapeutic approach in the treatment of stroke. FINDINGS: In this study, we indicated that a novel natural anti-oxidant extracted from the Chinese plant Hopea hainanensis, malibatol A (MA), decreased the infarct size and alleviated the brain injury after mice middle cerebral artery occlusion (MCAO). MA inhibited expression inflammatory cytokines in not only MCAO mice but also lipopolysaccharide (LPS)-stimulated microglia. Moreover, treatment of MA decreased M1 markers (CD16, CD32, and CD86) and increased M2 markers (CD206, YM-1) while promoting the activation of nuclear receptor PPARγ. CONCLUSIONS: MA has anti-inflammatory effects in MCAO mice in a PPARγ-dependent manner, making it a potential candidate for stroke treatment.

CYP2C19 polymorphisms and antiplatelet effects of clopidogrel in acute ischemic stroke in China.

BACKGROUND AND PURPOSE: Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke. METHODS: A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated. RESULTS: The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance. CONCLUSIONS: CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.

Association between CYP19 gene SNP rs2414096 polymorphism and polycystic ovary syndrome in Chinese women.

BACKGROUND: Several studies have reported the association of the SNP rs2414096 in the CYP19 gene with hyperandrogenism, which is one of the clinical manifestations of polycystic ovary syndrome (PCOS). These studies suggest that SNP rs2414096 may be involved in the etiopathogenisis of PCOS. To investigate whetherthe CYP19 gene SNP rs2414096 polymorphism is associated with the susceptibility to PCOS, we designed a case-controlled association study including 684 individuals. METHODS: A case-controlled association study including 684 individuals (386 PCOS patients and 298 controls) was performed to assess the association of SNP rs2414096 with PCOS. Genotyping of SNP rs2414096 was conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results. RESULTS: The genotypic distributions of rs2414096 (GG, AG, AA) in the CYP19 gene (GG, AG, AA) in women with PCOS (0.363, 0.474, 0.163, respectively) were significantly different from that in controls (0.242, 0.500, 0.258, respectively) (P = 0.001). E2/T was different between the AA and GG genotypes. Age at menarche (AAM) and FSH were also significantly different among the GG, AG, and AA genotypes in women with PCOS (P = 0.0391 and 0.0118, respectively). No differences were observed in body mass index (BMI) and other serum hormone concentrations among the three genotypes, either in the PCOS patients or controls. CONCLUSIONS: Our data suggest that SNP rs2414096 in the CYP19 gene is associated with susceptibility to PCOS.

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Under the positive human land use regulation (e.g. afforestation), understanding the impacts of landscape pattern changes on urban and rural thermal fields can provide reference data for future construction and optimization of urban afforestation projects and bring new insights for future landscape patterns and thermal fields environment related research. Under the context of "One Million Mu Plain Afforestation Project" in Beijing plain area, we applied remote sensing technology and geographic information system and used transfer-matrix method and coupling analysis to evaluate the impacts of plain afforestation on thermal field environment and to explore the correlation between changes in landscape patterns resulted from urban afforestation projects and urban land surface temperature. Our results showed that the percentage of landscape (PLAND) of forests and parks increased by 7.6% and 0.5% after the afforestation project in Beijing plain area, respectively. The heat island intensity decreased by 19.2% of entire plain area, and by 23.3% of suburban area, however, it increased by 23.5% of city area. Spanning urban to urban-rural interface, the PLAND of forests and parks, the mean patch size (MPS) of forests and wetlands were significantly negatively correlated with the changes in landscape surface temperature (LST). In city area, the area-weighted mean shape index (AWMSI) of forests was significantly positively correlated with the changes of LST. In suburban area, the MPS and AWMSI of forests showed significantly negative correlation with changes of LST, which was contrary to parks. After the implementation of afforestation project in Beijing plain area, the increased urban forests and urban parks had mitigated thermal fields to some extent. The scale of mitigation was limited and most areas with decreased heat island intensity were concentrated in newly planted sites in suburban area. The more connected the forests and wetlands, the better the relief of the thermal fields in the plain area. Impacted by the grain size, time, topography, human activities and other factors, the change in landscape patterns caused by the control of land use structure showed non-linear correlation with the change of LST.

Roles of sigma-1 receptors in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of senile dementia all over the world. Still no existing drugs can effectively reverse the cognitive impairment. However, Sigma-1 (σ-1) receptors have been long implicated in multiple neurological and psychiatric conditions over these years. In this review, we discuss the current understanding of σ-1 receptor functions. Through regulation of lipid rafts, secretases, kinases, neuroceptors and ion channels, σ-1 receptors can influence cellular signal transduction, TCA cycle, oxidative stress, neuron plasticity and neurotransmitter release etc. Based on this, we suggest the key cellular mechanisms linking σ-1 receptor to Alzheimer's disease. Besides, we detail the evidences showing that σ-1 receptors agonists, being the promising compounds for treatment of cognitive dysfunction, exhibit robust neuroprotection and anti-amnesia effect against Aß neurotoxicity in the progress of Alzheimer's disease. The evidence comes from animal models, preclinical studies in humans and full clinical trials. In addition, the questions to be solved regarding this receptor are also presented. When concerned with NMDAR, σ-1 receptor activation may result in two totally different influences on AD. Utilization of σ-1 agents early in AD remains an overlooked therapeutic opportunity. This article may pave the way for further studies about sigma-1 receptor on Alzheimer's disease.

CART treatment improves memory and synaptic structure in APP/PS1 mice.

Major characteristics of Alzheimer's disease (AD) include deposits of ß-amyloid (Aß) peptide in the brain, loss of synapses, and cognitive dysfunction. Cocaine- and amphetamine-regulated transcript (CART) has recently been reported to attenuate Aß-induced toxicity. In this study, CART localization in APP/PS1 mice was characterized and the protective effects of exogenous CART treatment were examined. Compared to age-matched wild type mice, 8-month-old APP/PS1 mice had significantly greater CART immunoreactivity in the hippocampus and cortex. A strikingly similar pattern of Aß plaque-associated CART immunoreactivity was observed in the cortex of AD cases. Treatment of APP/PS1 mice with exogenous CART ameliorated memory deficits; this effect was associated with improvements in synaptic ultrastructure and long-term potentiation, but not a reduction of the Aß plaques. Exogenous CART treatment in APP/PS1 mice prevented depolarization of the mitochondrial membrane and stimulated mitochondrial complex I and II activities, resulting in an increase in ATP levels. CART treatment of APP/PS1 mice also reduced reactive oxygen species and 4-hydroxynonenal, and mitigated oxidative DNA damage. In summary, CART treatment reduced multiple neuropathological measures and improved memory in APP/PS1 mice, and may therefore be a promising and novel therapy for AD.

Diammonium glycyrrhizinate attenuates Aß(1-42) -induced neuroinflammation and regulates MAPK and NF-κB pathways in vitro and in vivo.

BACKGROUND AND PURPOSE: Beta-amyloid (Aß)-mediated inflammation contributes to the progression and chronicity of Alzheimer's disease (AD), although the exact mechanism remains unclear. This study aimed to investigate whether diammonium glycyrrhizinate (DG) could inhibit Aß-induced inflammation in vitro and in vivo and to explore the underlying mechanisms. METHODS: Aß(1-42) was injected to bilateral hippocampus of mice to make the AD models in vivo. The levels of mRNA and protein of inflammatory cytokines were measured by real-time PCR and Western blotting, respectively. The viability of SH-SY5Y and HT-22 cells was determined by MTT. NF-κB p65 translocation was analyzed by Western blotting and immunostaining. Phosphorylation of ERK, p38, and JNK was tested by Western blotting. RESULTS: DG suppressed Aß(1-42) -induced activation of microglia and inflammation in vitro and in vivo. The media from Aß(1-42) -activated microglia decreased the viability of SH-SY5Y and HT-22 cells, but it was rescued when pretreated with DG. DG could inhibit the activation of MAPK and NF-κB signaling pathways and attenuate the memory deficits in Aß(1-42) -induced AD mice. CONCLUSIONS: DG protects Aß(1-42) -induced AD models in vitro and in vivo through reducing activation of microglia and inflammation, which may be involved in MAPK and NF-κB pathways.

Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia.

Hereditary spinocerebellar ataxia (SCA) is a devastating, incurable disease. Stem-cell-based therapies represent new promise for clinical research in neurology. The objectives of this study were to assess the feasibility, efficacy, and potential toxicity of human umbilical cord mesenchymal stem cells (UCMSCs) therapy in patients with SCA. Sixteen genomically diagnosed SCA patients were enrolled and received intravenous and intrathecal infusion of UCMSCs. Clinical, laboratory, and radiographic evaluations were conducted to assess the safety of UCMSC therapy. Efficacy was evaluated by the Berg Balance Scale (BBS) and International Cooperative Ataxia Rating Scale (ICARS) scores. Among the 16 cases, there were no serious transplant-related adverse events happened in 12 months follow-up. The majority of patients showed improved BBS and ICARS scores continuing for at least 6 months which indicated UCMSC therapy could alleviate SCA symptoms. This study suggested that UCMSC transplantation was safe and might delay the progression of SCA. This may represent a new therapeutic strategy for SCA and other genetic neurological diseases.

Clinical study on effect of HCL combined with Bromine Hydrochloride on infantile cough / 药物评价研究

Objective To investigate the clinical effect of ambroxol hydrochloride combined with cough syrupintegrated traditional Chinese and Western Medicine on infantile cough.Methods Selected 200 cases of patients with cough who were treated in our hospital from January 2012 to December 2015,divided into two groups randomly,100 cases in observation group,100 cases in control group.The observation group was treated with ambroxol hydrochloride combined with cough syrup,the control group were treated with ambroxol hydrochloride.To observe the clinical symptoms and clinical manifestations of the patients after treatment,recorded the time of cough and the disappearance of cough,and to determine the effect of treatment.The lung function indexes of the two groups were detected:peak expiratory flow,forced vital capacity,forced expiratory volume in one second,maximal expiratory flow rate of 50％ vital capacity and maximal expiratory flow rate of 25％ vital capacity.All the patients were followed up for 6 months by telephone or clinic,the recurrence rate of the two groups was observed,and the number of children with asthma were recorded.Results The time of cough and the disappearance time of cough in observation group were significantly shorter than that of the control group (P ＜ 0.05);the total effective rate of observation group was 93.00％ (93/100),significantly higher than that of the control group 74.00％ (74/100) (P ＜ 0.05).After treatment,expiratory flow peak,forced vital capacity,one second forced expiratory volume,vital capacity 50％ of maximum expiratory flow and 25％ of vital capacity maximal expiratory flow of two groups were significantly increased (P ＜ 0.05) and the observation group increased more significantly than the control group (P ＜0.05).After 6 months of follow-up,the control group had 22 cases of recurrence,the recurrence rate was 22.00％;the observation group had 6 cases of recurrence,the recurrence rate was 6.00％,the recurrence rate of the observation group was significantly lower than that of the control group (P ＜ 0.05);the control group had 14 cases of children with asthma,the change rate was 14％;the observation group had 2 cases of children with asthma,the change rate was 2％,the change rate of the observation group was significantly lower than that of the control group (P ＜ 0.05).Conclusion Ambroxol hydrochloride combined with cough syrup has better curative effect on infantile cough,can effectively improve children's lung function,reduce the rate of recurrence and change of asthma,which has high clinical application value.

Clinical study on effect of HCL combined with Bromine Hydrochloride on infantile cough / 药物评价研究

Objective To investigate the clinical effect of ambroxol hydrochloride combined with cough syrupintegrated traditional Chinese and Western Medicine on infantile cough.Methods Selected 200 cases of patients with cough who were treated in our hospital from January 2012 to December 2015,divided into two groups randomly,100 cases in observation group,100 cases in control group.The observation group was treated with ambroxol hydrochloride combined with cough syrup,the control group were treated with ambroxol hydrochloride.To observe the clinical symptoms and clinical manifestations of the patients after treatment,recorded the time of cough and the disappearance of cough,and to determine the effect of treatment.The lung function indexes of the two groups were detected:peak expiratory flow,forced vital capacity,forced expiratory volume in one second,maximal expiratory flow rate of 50％ vital capacity and maximal expiratory flow rate of 25％ vital capacity.All the patients were followed up for 6 months by telephone or clinic,the recurrence rate of the two groups was observed,and the number of children with asthma were recorded.Results The time of cough and the disappearance time of cough in observation group were significantly shorter than that of the control group (P ＜ 0.05);the total effective rate of observation group was 93.00％ (93/100),significantly higher than that of the control group 74.00％ (74/100) (P ＜ 0.05).After treatment,expiratory flow peak,forced vital capacity,one second forced expiratory volume,vital capacity 50％ of maximum expiratory flow and 25％ of vital capacity maximal expiratory flow of two groups were significantly increased (P ＜ 0.05) and the observation group increased more significantly than the control group (P ＜0.05).After 6 months of follow-up,the control group had 22 cases of recurrence,the recurrence rate was 22.00％;the observation group had 6 cases of recurrence,the recurrence rate was 6.00％,the recurrence rate of the observation group was significantly lower than that of the control group (P ＜ 0.05);the control group had 14 cases of children with asthma,the change rate was 14％;the observation group had 2 cases of children with asthma,the change rate was 2％,the change rate of the observation group was significantly lower than that of the control group (P ＜ 0.05).Conclusion Ambroxol hydrochloride combined with cough syrup has better curative effect on infantile cough,can effectively improve children's lung function,reduce the rate of recurrence and change of asthma,which has high clinical application value.