Inhibition of sugar-binding activity of Galectins-8 by thiogalactoside (TDG) attenuates secondary brain damage and improves long-term prognosis following intracerebral hemorrhage.

Galectins-8 (Gal-8), the tandem repeat sequences of the galectin family, can influence the pathophysiologic processes in neurological disorders. However, its effect on intracerebral hemorrhage and related mechanisms remains nebulous. Using collagenase VII-S-induced ICH in the left striatum of mice, we investigated the effects of Gal-8 on cellular and molecular immune inflammatory responses in hemorrhagic brain and evaluated the severity of short- and long-term brain injury. Our results showed that activated microglia in the periphery of hematoma in mice with intracerebral hemorrhage expressed Gal-8, while Gal-8 could regulate the expression of cytokines, such as HMGB-1 (P = 0.0032), TNF-α (P = 0.0158), and IL-10 (P = 0.0379). Inhibition of the glucose-binding activity of Gal-8 by thiogalactoside (TDG) significantly reduced the volume of cerebral hematoma (P = 0.0241) and hydrocephalus (P = 0.0112) during the acute phase of cerebral hemorrhage and improved the long-term prognosis. TDG can reduce acute-phase brain tissue injury and improve the prognosis by inhibiting the activation of immune-inflammatory cells in the periphery of hematoma and reducing the release of pro-inflammatory factors.

Overexpression of C9orf72 exacerbates Aß25­35­induced oxidative stress and apoptosis in PC12 cells.

Alzheimer's disease (AD) is the most common neurodegenerative disease and is manifested by memory loss and spatial disorientation. There is currently no effective treatment for AD. Abnormalities of the chromosome 9 open reading frame 72 (C9ORF72) gene have been associated with various neurodegenerative diseases. However, its intrinsic roles in AD remain to be elucidated. Here we found that Aß25­35 increased the expression of C9orf72 in PC12 cells at both mRNA and protein levels. In Aß25­35­treated PC12 cells, C9orf72 overexpression induced an abnormally condensed and fragmented nucleus and apoptosis, as well as significantly enhanced reactive oxygen species (ROS) levels. Mechanistically, an Aß25­35­induced decrease of superoxide dismutase activity was augmented by C9orf72 overexpression, which in contrast increased malondialdehyde content. Consistently, further apoptotic analysis revealed significant downregulation of Bcl­2 and Bcl­xL expression and enhanced cleavage of caspase­3 with Aß25­35 treatment, all of which were exacerbated by C9orf72 overexpression. In addition, tau phosphorylation, another hallmark of AD pathology, was induced by Aß25­35 and was remarkably enhanced by C9orf72 overexpression. Our data indicate that C9orf72 plays important roles in intracellular ROS signaling and Aß25­35­induced neuronal apoptosis in AD. These findings provide insights into C9orf72 function in the pathogenesis of many related neurodegenerative diseases and provide a basis for potential therapeutic interventions.

Ischemic Preconditioning Induces Oligodendrogenesis in Mouse Brain: Effects of Nrf2 Deficiency.

Ischemic preconditioning (IPC) is an approach of protection against cerebral ischemia by inducing endogenous cytoprotective machinery. However, few studies in neurogenesis and oligodendrogenesis after IPC have been reported, especially the latter. The purpose of this study is to test our hypothesis that IPC may also induce cell proliferation and oligodendrogenesis in the subventricular zone and striatum, as well as to investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) on oligodendrogenesis. IPC was induced in mice by 12-min ischemia through the occlusion of the middle cerebral artery. Newly generated cells were labeled with 5-bromo-2'-deoxyuridine. Our findings demonstrated that IPC stimulated the proliferation of neural stem cells in the subventricular zone, promoted the generation of oligodendrocyte precursor cells in the striatum and corpus callosum/external capsule (CC/EC), and stimulated oligodendrocyte precursor cells differentiation into oligodendrocytes in the striatum and the CC/EC. Furthermore, we describe a crucial role for Nrf2 in IPC-induced oligodendrogenesis in the subventricular zone, striatum, and CC/EC and show for the first time that Nrf2 promoted the migration and differentiation of oligodendrocyte precursor cells into oligodendrocytes in the striatum and CC/EC. Our data imply that IPC stimulates the oligodendrogenesis in the brain and that Nrf2 signaling may contribute to the oligodendrogenesis.

[Analysis of age-specific cytogenetic changes among 515 patients withacute myeloid leukemia].

OBJECTIVE: To characterize cytogenetic changes and prognosis of patients with acute myeloid leukemia (AML) from different age groups. METHODS: The karyotypes of 515 AML patients were analyzed by using short-term culture of bone marrow cells and R-banding technique. Combined with FAB typing and genetic testing, cytogenetic changes and prognosis of different age groups were analyzed. RESULTS: The abnormal cloning rate was 54.6% among the 515 patients. The abnormal cloning rate and adverse risk karyotype proportion of those with myeloproliferative syndromes (MDS) and secondary AML were higher than those with de novo AML (P = 0.027; P<0.01). A significant difference was found in the number of structural abnormalities and proportion of favorable risk karyotypes among different age groups (P = 0.026; P = 0.004). And there was also a significant difference in the abnormal cloning rate between different FAB types (P<0.01). In those with non-acute promyelocytic leukemia (APL), the expression level of WT1 gene seemed to affect the prognosis. The survival rate of patients with karyotypes of adverse risk was lower than those with karyotypes of favorable risk (P = 0.015). The survival rate of the ≥60-year-old group was lower than the ≤30-year-old and 31 to 59-year-old groups (P<0.01, P<0.01). CONCLUSION: The karyotypes of AML patients have different age distribution characteristics. The survival rate of ≥60-years-old group and karyotype of poor prognosis is low. Patients with MDS with secondary AML have a poor prognosis.

Morphological parameters and anatomical locations associated with rupture status of small intracranial aneurysms.

Characterization of the rupture risk factors for small intracranial aneurysms (SIAs, ≤5 mm) is clinically valuable. The present study aims to identify image-based morphological parameters and anatomical locations associated with the rupture status of SIAs. Two hundred and sixty-three patients with single SIAs (128 ruptured, 135 unruptured) were included, and six morphological parameters, including size, aspect ratio (AR), size ratio (SR), height-width ratio (H/W), flow angle (FA) and aneurysm width-parent artery diameter ratio, and the aneurysm locations were evaluated using three-dimensional geometry, and were used to identify a correlation with aneurysm rupture. Statistically significant differences were observed between ruptured and unruptured groups for AR, SR, H/W, FA, and aneurysm locations, from univariate analyses. Logistic regression analysis further revealed that AR (p = 0.034), SR (p = 0.004), H/W (p = 0.003), and FA (p < 0.001) had the strongest independent correlation with ruptured SIAs after adjustment for age, gender and other clinical risk factors. A future study on a larger SIA cohort need to establish to what extent the AR, SR, H/W and FA increase the risk of rupture in patients with unruptured SIAs in terms of absolute risks.

RNA interference-mediated silencing of S100B improves nerve function recovery and inhibits hippocampal cell apoptosis in rat models of ischemic stroke.

Ischemic stroke is the leading cause of worldwide mortality and long-term disability in adults. This study aims to explore the effects of RNA interference (RNAi)-mediated silencing of the S100B gene on nerve function recovery and morphological changes of hippocampus cells in rat models with ischemic stroke. Sixty Wistar rats were assigned into different group. S100B and Caspase 3 mRNA and protein expressions were evaluated by RT-qPCR and Western blotting. Positive rate of S100B, NeuN, and MAP2 expressions were detected by immunohistochemistry (IHC). Water content, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity in brain tissues were measured. Enzyme-linked immunosorbent assay (ELISA) was employed to detect serum levels of TNF-α and IL-1ß. A neurological severity score (NSS) was used to test nerve function. TUNEL assay was used to determine hippocampal cell apoptosis. Downregulation of S100B showed a lower number of S100B immune positive cells, but higher NeuN and MAP2-positive cells, increased SOD level, declined MDA level, prominently faster recovery of neurological function, decreased TRCS, TCTP, TCFP, and IE levels, an obvious increase in the number of survival neurons, a decrease in the number of apoptotic cells, notably decreased TNF-α and IL-1ß contents, as well as infarct volume, an obvious decrease in positive hippocampal cell Caspase 3 expression and protein expressions of Caspase 3 and cleaved Caspase 3. This study provides data to suggest that RNAi-mediated silencing of S100B gene could improve the recovery of nerve function while inhibiting apoptosis of hippocampal cells in rats with ischemic stroke.

Transorbital Doppler with carotid siphon monitoring detects right-to-left shunt effectively.

Background Transtemporal Doppler (TTD) with middle cerebral artery (MCA) is widely used for right-to-left shunt (RLS) detection. However, an alternative method for patients without suitable temporal bone windows should be established. The present study prospectively evaluated the effectiveness of transorbital Doppler (TOD) with carotid siphon (CS) monitoring in detecting RLS. Methods A total of 357 subjects with sufficient temporal bone windows underwent simultaneous TTD with MCA and TOD with CS. After injection of microbubbles, the numbers of artificial high-intensity signals were recorded at rest and after Valsalva maneuver. Results TOD with CS detected RLS in 146 patients. Sensitivity was 97.1%, specificity 95%, positive predictive value 92.5%, and negative predictive value 98.1%. The total positive rates for RLS detection by CS (40.9%) and MCA (37.8%) monitoring were comparable without significant difference, but TOD with CS detected significantly more grade 2 and 3 RLS than TTD with MCA (p = 0.001). The RLS rates of cryptogenic stroke patients was significantly higher than that of healthy controls, and RLS in cryptogenic stroke was remarkably higher than that in transient ischemia attack patients (p < 0.05). TOD with CS examined significantly more grade 2 and 3 RLSs than the MCA approach in the cryptogenic stroke patients (p = 0.037). Conclusion TOD with CS monitoring is able to detect RLS effectively in different populations including healthy subjects, cryptogenic stroke, transient ischemia attack, and migraine patients. In comparing to the TTD with MCA approach, TOD with CS monitoring could detect comparable rate of RLS, but more high grades of RLS.

Bioinformatics analysis of gene expression profiling for identification of potential key genes among ischemic stroke.

This study aimed to identify the key differentially expressed genes (DEGs) following ischemic stroke (IS).The GSE22255 microarray dataset, which contains samples from peripheral blood mononuclear cells of 20 IS patients and 20 sex- and age-matched controls, was downloaded from the Gene Expression Omnibus. After data pre-processing, DEGs were identified using the Linear Models for Microarray Data package in R. The Search Tool for the Retrieval of Interacting Genes database was used to predict the interactions among the products of DEGs, and then Cytoscape software was used to visualize the protein-protein interaction (PPI) network. DEGs in the PPI network were then analyzed using the Database for Annotation, Visualization, and Integrated Discovery online software to predict their underlying functions through functional and pathway enrichment analyses.A total of 144 DEGs were identified in IS samples compared with control samples, including 75 upregulated and 69 downregulated genes. Genes with higher degrees in the PPI network included FOS (degree = 26), TP53 (degree = 22), JUN (degree = 20), EGR1 (degree = 18), JUNB (degree = 16), and ATF3 (degree = 15), and these genes may function in IS by interacting with each other (e.g., EGR1-JUN, EGR1-TP53, ATF3-FOS, and JUNB-FOS). Functional enrichment analysis indicated that the downregulated TP53 gene was enriched in immune response and protein targeting categories.ATF3 and EGR1 may have an important protective effect on IS, whereas FOS, JUN, and JUNB may be associated with the development of IS. In addition, TP53 may function as an indicator of poor prognosis for IS through its association with the immune response and protein targeting.

[Detection of genomic abnormalities among 105 patients with chronic lymphocytic leukemia using fluorescence in situ hybridization].

OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) for the detection of genomic abnormalities among patients with chronic lymphocytic leukemia (CLL). METHODS: Interphase FISH was performed on bone marrow samples derived from 105 patients with CLL at the time of diagnosis using probes for D13S319/13q14, ATM/11q22, P53/17p13 and CEP12. The abnormalities and prognostic factors were analyzed. Overall survival of the patients was calculated. RESULTS: The FISH assay has detected genomic abnormalities in 81 (77.1%) of the patients, among which D13S319/13q14 deletion was the most common (49/105, 46.67%). 24(22.86%) patients had trisomy 12, 21(20.00%) had ATM/11q deletion, and 12(11.43%) had P53/17p deletion. A significant correlation was found between Binet staging and the detected abnormalities (< 0.05). With a median follow-up time of 10 months, 11 patients (10.5%) had died. Compared with those with P53 deletion, patients with 13q deletion showed a better overall survival. However, the overall survival did not significantly differ between patients with various genomic abnormalities (> 0.05). CONCLUSION: FISH is capable of detecting common genomic aberrations among patients with newly diagnosed CLL. Deletion of D13S319/13q14 is the most common aberration in such patients. Genomic aberrations are significantly correlated with Binet staging but not the overall survival of CLL patients.

Oxysophocarpine reduces oxygen-glucose deprivation-induced microglial activation and injury.

Microglial over-activation and apoptosis are associated with ischemic brain diseases. These processes may be hindered by oxysophocarpine (OSC) that generates anti-inflammatory and anti-apoptotic activities. However, the precise roles of OSC in microglial inflammation and apoptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R) remain unclear. In this study, we found that OSC reduced OGD/R-induced inflammation in BV-2 microglia. OSC elevated cell viability and prevented the release of lactate dehydrogenase. OSC downregulated cyclooxygenase 2 and inducible nitric oxide synthase and reduced the levels of inflammatory mediators, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1, prostaglandin E2, and nitric oxide. OSC inhibited the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) and blocked the activation of nuclear factor (NF)-κB. In addition, OSC suppressed OGD/R-elicited BV-2 cell apoptosis, as indicated as follows: The restored mitochondrial membrane potential and the reduced caspase-3 activity; the decrease of Bax and cleaved caspase-3 and the increase of Bcl-2; the enhanced phosphorylation of Akt and mTOR. These results implied that OSC impedes OGD/R-induced inflammation and apoptosis of microglial cells. Therefore, OSC may be potentially used for ischemic stroke therapy.

Ethyl pyruvate protects PC12 cells from oxygen-glucose deprivation: A potential role in ischemic cerebrovascular disease.

The protective potential of ethyl pyruvate (EP) on neuron has been investigated previously. This study was intended to investigate the effects of EP on the severity of oxygen-glucose deprivation (OGD)-induced injury in neural-like PC12 cells. PC12 cells were exposed to OGD condition with or without EP treatment. Then, cell viability, apoptosis, and the expressions of neurotrophic factors were detected. Further, Sprague-Dawley rats were intravenously administered with 5mg/kg EP for 14 days post-middle cerebral artery occlusion (MCAO). The effects of EP on the infarct volumes and neurological functions of MCAO rats were then assessed. Result showed that EP alleviated OGD-diminished cells viability, OGD-induced apoptosis, and OGD-reduced expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and Nestin in PC-12 cells. EP blocked OGD-activated the Notch1 and nuclear factor Kappa B (NF-κB) signaling pathways in PC12 cells. Besides, in vivo data demonstrated that EP treatment decreased infarct volume and mNSS score, and increased the time spent on the rota-rod apparatus of MCAO rats. To conclude, EP protected neural-like PC12 cells from cerebral ischemia-reperfusion injury by suppressing apoptosis and promoting neural restoration. Notch1 and NF-κB pathway might implicated in the functions of EP on neuron.

Association of MicroRNA-146a and MicroRNA-149 Polymorphisms With Strokes in Asian Populations: An Updated Meta-Analysis.

Strokes are a major cause of disability and death worldwide. An association between microRNA-146a (miR-146a) and miR-149 polymorphisms and strokes was inconclusive. This meta-analysis aimed to reevaluate the strength of the association by searching online databases and retrieving relevant case-control studies published between 2000 and 2016. Nine articles including 8 on miR-146a rs2910164 G/C and 3 on miR-149 rs2292832 C/T in 3372 patients with stroke and 4394 controls were included. The miR-149 rs2292832 was significantly associated with the risk of a stroke under allelic (C vs T: odds ratio [OR] = 1.14; 95% confidence interval [CI] = 1.01-1.29; P = .03), homologous (CC vs TT: OR = 1.36; 95% CI = 1.05-1.77; P = .02), and recessive models (CC vs CT + TT: OR = 1.34; 95% CI = 1.05-1.71; P = .02). No correlation was detected between miR-146a rs2910164 and susceptibility to a stroke. In conclusion, the results suggested that miR-149 might be a risk factor for the development of a stroke, while miR-146a might not be. Well-designed studies with large populations are needed to clarify the association between miR-146a and miR-149 polymorphisms and strokes.

Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke.

Epigallocatechin-3-gallate (EGCG) is the major effective component of green tea and has been known as a potential anticancer drug because of its antioxidant and anti-angiogenic properties. EGCG has also been reported to have preventive effects against ischemic stroke via nuclear factor erythroid 2-related factor 2 (Nfr2) signaling pathway, but how EGCG affect angiogenesis after stroke remains unclear. In this study, we investigated whether EGCG treatment in the acute phase of ischemic stroke can promote angiogenesis in a mouse model of transient middle cerebral artery occlusion (MCAO). We assessed neurological function with modified neurologic severity score (mNSS) test, infarct volume by Nessl staining, angiogenesis and oxidative stress by immunofluorescence analysis, intravital lectin perfusion analysis, western blot analysis and enzyme-linked immunosorbent assay (ELISA). In order to explore the role of Nrf2 in the angiogenesis of MCAO+EGCG-treated mice, we used MAPK/ERK inhibitor PD98059 to block the activation of Nrf2. We found MCAO+EGCG-treated mice had better neurologic outcome, less infarct volume, more number of Ki67/CD31-positive vessels, higher vascular density, unregulated VEGF-VEGFR2 signaling pathway, increased Nrf2 expression and decreased oxidative stress than did MCAO+vehicle-treated mice. Blocking Nrf2 with PD98059 significantly reduced the expression of Nrf2, increased oxidative stress and abolished the angiogenic and neuroprotective effects of EGCG on MCAO mice. We conclude that EGCG treatment in the early stage of ischemic stroke can promote angiogenesis in MCAO mice, possibly via upregulation of Nrf2 signaling pathway.

Increased Expression of mir-34a-5p and Clinical Association in Acute Ischemic Stroke Patients and in a Rat Model.

BACKGROUND MiRNA is widely recognized as the most important regulator in various diseases. However, there has been little research regarding miRNA expression and its involvement in ischemic stroke. MATERIAL AND METHODS In this study, we investigated the pattern of miRNA-34a-5p expression along with its clinical application in human ischemic stroke and in an in vivo rat model. We recruited 102 cerebral ischemia patients and 97 health controls for this study. Clinical data were gathered and recorded with the help of questionnaires. Blood samples were obtained from patients within 72 h after cerebral ischemia. National Institutes of Health Stroke Scale (NIHSS), Acute Stroke Treatment (TOAST), and infarct volume were used to analyze the correlation of miRNA-34a-5p expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion (MCAO) model consisting of 20 adult male mice at 24 h after the MCAO. Expression level of miRNA-34a-5p was detected by real-time polymerase chain reactions. RESULTS Results showed overexpression of miRNA-34a-5p in acute ischemic stroke patients blood samples compared to the controls (p<0.05). Also, large and small arterial strokes types demonstrated elevated miRNA-34a-5p expression levels. Further correlation analysis revealed a negative association between miRNA-34a-5p and NIHSS scores (r=-0.692 p<0.05) and infarct volume (r=-0.719, p<0.05). Moreover, in vivo experiment results showed significant up-regulated expression of miRNA-34a-5p in middle cerebral artery occlusion compared to controls, along with a positive correlation between miRNA-34a-5p in blood and brain (r=0.742, p<0.05). CONCLUSIONS Our results suggest there is a potential regulatory role of miRNA-34a-5p in acute ischemic stroke, which could serve as a therapeutic target or biomarker in stroke prognosis.

Effects of caffeic acid on learning deficits in a model of Alzheimer's disease.

Caffeic acid is a type of phenolic acid and organic acid. It is found in food (such as tomatoes, carrots, strawberries, blueberries and wheat), beverages (such as wine, tea, coffee and apple juice) as well as Chinese herbal medicines. In the present study, we examined the effects of caffeic acid on learning deficits in a rat model of Alzheimer's disease (AD). The rats were randomly divided into three groups: i) control group, ii) AD model group and iii) caffeic acid group. Caffeic acid significantly rescued learning deficits and increased cognitive function in the rats with AD as demonstrated by the Morris water maze task. Furthermore, caffeic acid administration resulted in a significant decrease in acetylcholinesterase activity and nitrite generation in the rats with AD compared with the AD model group. Furthermore, caffeic acid suppressed oxidative stress, inflammation, nuclear factor­κB­p65 protein expression and caspase­3 activity as well as regulating the protein expression of p53 and phosphorylated (p-)p38 MAPK expression in the rats with AD. These experimental results indicate that the beneficial effects of caffeic acid on learning deficits in a model of AD were due to the suppression of oxidative stress and inflammation through the p38 MAPK signaling pathway.

Geniposide reduces α-synuclein by blocking microRNA-21/lysosome-associated membrane protein 2A interaction in Parkinson disease models.

OBJECTIVE: This study aimed to explore whether the regulatory effect of miR-21 on α-synuclein expression in neurons is a potential mechanism by which geniopside (GP) protects the central nervous system from Parkinson disease (PD). METHODS: The human neuroblastoma cell line SH-SY5Y was induced to differentiate in vitro and treated with dimethyl sulfoxide (DMSO), N-methyl-4-phenylpyridinium iodide (MPP(+)), and MPP(+) together with GP. To identify the role of miR-21 in the regulation of lysosome-associated membrane protein 2 (LAMP2A) and α-synuclein, SH-SY5Y cells pretreated with MPP(+) were transfected with miR-21 mimic and miR-21 inhibitor. To identify whether GP could reduce the level of α-synuclein through miR-21/LAMP2A, SHSY5Y cells pretreated with GP were treated with miR-21 mimic or miR-21 inhibitor; meanwhile, a luciferase reporter assay was performed to confirm the direct target of miR-21. LAMP2A was overexpressed using a pCMV6-XL5-LAMP2A vector to confirm the role of LAMP2A in the regulation of α-synuclein by miR-21. In these in vitro experiments, the RNA and/or protein expressions of miR-21, LAMP2A, and α-synuclein in SH-SY5Y cells were determined by quantitative real-time polymerase chain reaction and/or western blotting, respectively. An in vivo PD mouse model was established through intraperitoneal injection with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). The mice were treated with saline, MPTP, MPTP+GP, and MPTP+GP+miR-21 agomir. The numbers of TH(+) cells in the substantia nigra in different groups of mice were compared. The RNA and/or protein expressions of miR-21, LAMP2A, and α-synuclein were also determined. RESULTS: The level of miR-21 in the cells or mice models was significantly higher than that in normal cells or normal mice, respectively, and GP significantly downregulated miR-21. GP also raised the protein and mRNA expressions of LAMP2A and reduced the protein level of α-synuclein in PD models. MiR-21 upregulated the expression of α-synuclein by directly targeting 3' UTR of LAMP2A. LAMP2A overexpression abolished the upregulating effect of miR-21 mimic on α-synuclein. MiR-21 mimics/agomir reversed the GP-induced downregulation of α-synuclein; miR-21 inhibitor effectively increased the downregulation of α-synuclein caused by GP. CONCLUSION: GP exhibits neuroprotective properties by inhibiting α-synuclein expression in PD models through the miR-21/LAMP2A axis.

MicroRNA-7 inhibits neuronal apoptosis in a cellular Parkinson's disease model by targeting Bax and Sirt2.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. MicroRNA-7 (miR-7) displays neuroprotective properties against PD. However, the biological roles of miR-7 and its underlying molecular mechanisms in PD remain unclear. We demonstrated herein that 1-methyl-4-phenylpyridinium ion (MPP(+)) confers toxic effects on dopaminergic neuron in a dose-dependent manner in a cellular PD model, although this phenomenon is attenuated by miR-7 treatment. Introduction of miR-7 inhibits MPP(+)-induced neuronal apoptosis as reflected by the reduced terminal transferase-mediated dUTP nick end labeling-positive rate, mitochondrial permeability potential, caspase 3 activity, and nucleosomal enrichment factor. Bax and sirtuin 2 (Sirt2) are the direct targets of miR-7. Moreover, the effects of miR-7 were counteracted by Bax and Sirt2 overexpression, respectively. The altered molecular expressions downstream of Bax and Sirt2 are also involved in miR-7 regulation of the MPP(+)-triggered neuronal apoptosis. These findings have implications on the potential application of miR-7 in PD treatment.

Complete mitochondrial genome sequence of the Rattus norvegicus SILN strain with central nervous system disorder.

The Rattus norvegicus SILN strain is a common used model for nervous system disorder disease study. We sequenced this R. norvegicus strain SILN mitochondrial genome for the first time (GenBank Accession No. KM114606). Its mitogenome was 16,311 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes.

[Clinical and cytogenetic study of chromosome 1 abnormality in myelodysplastic syndrome].

OBJECTIVE: To explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome（MDS）to couple its association with clinical presentation and prognosis. METHODS: R- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis. RESULTS: Of 672 cases of patients with MDS, chromosome 1 aberrationï¼»der（1）, dup（1）, －1 were most frequentï¼½ were found in 41（6.1%）cases. 1q trisomy was found in 18/41（43.9%）cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18（0.56-54.28）months. Median survival of 36 cases after 2010 was 17.48（95% CI 14.38-20.58）months. There were significant differences on median survival between RAEB and non-RAEB groups（χ²=10.398, P=0.001）, and between with more than 3 chromosome abnormalities and with less than 3 groups（χ²=3.939, P=0.047）. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality. CONCLUSION: Chromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.

Expression of ß-site APP-cleaving enzyme 1 in the hippocampal tissue of an insulin-resistant rat model of Alzheimer's disease.

The aim of this study was to investigate the expression of ß-site APP-cleaving enzyme 1 (BACE1) in the hippocampal tissue of an insulin-resistant rat model, and thereby explore the roles of BACE1 and insulin resistance (IR) in the pathogenesis of Alzheimer's disease (AD). A total of 36 male Sprague-Dawley rats, aged 2 months, were randomly divided into three groups. These were an insulin-resistant (experimental) group, a high fat control group and a blank control group. The cognitive function and behavioral changes of the rats were tested by a Morris water maze experiment. Amyloid ß (Aß) deposition was detected by an immunohistochemical method. The expression levels of BACE1 in the rat hippocampal tissues were detected by enzyme-linked immunosorbent assay, western blotting and reverse transcription-quantitative polymerase chain reaction technology. The rats in the experimental group had evident learning and memory impairment, with significantly decreased learning memory. The modeling was successful; in the experimental group, the rats exhibited IR and their glucose metabolism was significantly abnormal. However, there was no characteristic pathology of AD. The expression of BACE1 in the brain tissue of rats in the experimental group was significantly higher than that in high fat control and blank control groups (P<0.01). In conclusion, the expression of BACE1 in the brain tissue of insulin-resistant rats increased, and IR was indicated to participate in the pathogenesis of AD.