MicroRNA-326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, and substantia nigra is primarily one of the damaged brain regions. Evidence indicates that microRNAs (miRNAs) is involved in the pathophysiology of this disease. The present study aimed to investigate the biological function of miR-326 in PD through the JNK signaling pathway by targeting X-box binding protein 1 (XBP1). After liposome complexes were prepared, healthy male C57BL/6 mice were selected to construct a mouse model of PD. The targeting relationship between miR-326 and XBP1 was confirmed. The expression of miR-326 and XBP1 was measured in PD mice, and gain- and loss-function assay was conducted to examine the regulatory effect of miR-326 and XBP1 on inducible nitric oxide synthase (iNOS) expression and autophagy of dopaminergic neurons of PD mice. Mice treated with miR-326 mimic and siRNA-XBP1 showed increased traction test scores, activation of autophagy, expression of LC3-II, c-Jun, and p-α-Syn, but diminished climbing time and expressions of iNOS, α-Syn, and p-c-Jun. The siRNA-XBP1 treatment could reverse the effect of miR-326 inhibitor on PD mice. Overexpression of miR-326 inhibits iNOS expression and promotes autophagy of dopaminergic neurons through JNK signaling by targeting XBP1.

Cathepsin K Knockout Exacerbates Haemorrhagic Transformation Induced by Recombinant Tissue Plasminogen Activator After Focal Cerebral Ischaemia in Mice.

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk-/- mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood-brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk-/- than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk-/- than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood-brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

Polydopamine/polyethyleneimine complex adhered to micrometer-sized magnetic carbon fibers for high-efficiency hemoperfusion.

Carbon-based nanomaterials have recently attracted tremendous attention in adsorption, separation and biological fields. However, such modification is not always straightforward when the surface is not chemically reactive. Given this reason, most carbon materials modification processes employ reactive linkers or coupling agents, which are complicated and time-consuming. Herein, we report on a dopamine-polyethyleneimine (PEI) coating strategy to fabricate micrometer-sized magnetic carbon fiber (MSMCF)-based extracorporeal blood-cleansing sorbent for hemoperfusion. Results showed that the dopamine/PEI-coated MSMCF had a twisted fiber shape with a size range of 80-120 µm in diameter and porous structure with a specific surface area of 146 m2 g-1. Adsorption behavior of dopamine/PEI-modified MSMCF was examined by using bilirubin as a toxin model compound. Equilibrium data were well fitted to the Langmuir isotherm model with a maximal adsorption capacity of 335.1 mg g-1 at ambient temperature. The as-obtained material had relatively high bilirubin adsorption selectivity against albumin at a normal albumin concentration. In particular, the dopamine/PEI-coated MSMCF has excellent adsorption capacity and hemocompatibility compared to the MSMCF decorated only by dopamine or PEI. Therefore, this work may pave the way for enhancing the property of the extracorporeal blood-cleansing sorbent during hemoperfusion.

Predictive role of CHADS2 and CHA2DS2-VASc scores on stroke and thromboembolism in patients without atrial fibrillation: a meta-analysis.

OBJECTIVE: CHA2DS2-VASc is the extension of the CHADS2 score developed by Birmingham 2009. This risk stratification schema is often used in clinical setting when considering additional risk factors for developing stroke in AF patients. However, its role in the non-AF population is unknown. This study was designed to evaluate the accuracy of the CHADS2 and the CHA2DS2-VASc scoring systems. METHODS: Studies designed for CHADS2 and CHA2DS2-VASc score in stratifying the risks for stroke development in non-AF patients were included. RESULTS: Among the 114 studies identified, six trials were chosen finally and included for meta-analysis. The pooled diagnostic odds ratio (DOR) for CHADS2 and CHA2DS2-VASc was 2.86 (95% CI =1.83-4.28) and 2.80 (95% CI =1.83-4.28), respectively. CHA2DS2-VASc score was of better sensitivity than CHADS2 score (0.920 vs. 0.768). However, both scores were showed to have inherent heterogeneity and poor specificity. CONCLUSIONS: Though having good diagnostic accuracy, the clinical application of the CHADS2 and CHA2DS2-VASc scores in predicting risk of stroke development in non-AF patients still needs further validation. Key message The overall diagnostic accuracy of CHADS2 and CHA2DS2-VASc in stroke-risk stratification was good in patients with non-atrial fibrillation.

Pulse pressure as an independent predictor of stroke: a systematic review and a meta-analysis.

BACKGROUND: Recent evidence suggests that pulse pressure (PP) is a strong cardiovascular diseases' risk factor. We systematically evaluated all relevant studies to determine whether PP can be used as an independent predictor of stroke and mortality. METHODS AND RESULTS: A meta-analysis was performed by searching the published literature using MEDLINE, Cochrane and Google Scholar databases up to December 15, 2015. We measured the effect size expressed by hazard ratio (HR) and 95 % confidence interval (95 % CI). Eleven publications were included in the analysis. Pooled results demonstrated that 10 mmHg increase in PP was associated with increased risk of stroke occurrence (pooled HR 1.046, 95 % CI 1.025-1.068, P < 0.001). Additionally, systolic blood pressure (SBP) (pooled HR 1.053, 95 % CI 1.033-1.073, P < 0.001) and diastolic blood pressure (DPB) (pooled HR 1.056, 95 % CI 1.038-1.074, P < 0.001) were found to be significant predictors for stroke. We did not find a significant association between PP and all-cause mortality (pooled HR 1.022, 95 % CI 0.983-1.063, P = 0.270). We found SBP (pooled HR 1.008, 95 % CI 1.002-1.014, P = 0.012), but not DBP (pooled HR 1.023, 95 % CI 0.964-1.085, P = 0.451) to be significantly associated with all-cause mortality. CONCLUSIONS: Current data confirms that PP is an independent risk factor for stroke but is not a predictor of mortality.

Determination of Silicon in Gasoline by Directly Measuring under Organic Phase Using Inductively Coupled Plasma Optical Emission Spectroscopy.

A simple and accurate method was developed for determining silicon in gasoline using inductively coupled plasma optical emission spectroscopy (ICP-OES). For sample inroduction a Burgener nubulizer and a Cyclonic spray chamber were used. A gasoline sample was diluted with isooctane and then introduced into the cooled spray chamber of the ICP-OES. Good linearity was achieved in the silicon concentration range 0.1 - 10.0 mg x kg(-1), and the correlation coefficient was 0.999 96. The detection limit for silicon was 0.012 mg x kg(-1) and the silicon recoveries from gasoline samples were 95.8% - 98.4%, with relative standard deviations of less than 3.0% The method was proved to be simple, reliable and highly sensitive, and suitable for determining silicon in samples of motor gasoline, ethanol-gasoline and methanol-gasoline fuel mixtures those containing not more than 15% (V/V) oxygenates.

Relationship between vertebral artery hypoplasia and posterior circulation stroke in Chinese patients.

INTRODUCTION: Vertebral artery hypoplasia (VAH), which has been found in about 10 % of normal individuals, does not produce symptoms but may be associated with an increased risk of cerebral posterior circulation ischemic (PCI) stroke. The aims of this study were to determine the prevalence of VAH in Chinese patients with cerebral infarction and investigate whether VAH is an independent risk factor for PCI stroke. METHODS: The medical records of 841 Chinese stroke patients were reviewed retrospectively. All patients underwent either cervical contrast-enhanced magnetic resonance angiography (CE-MRA) or cervical computed tomography angiography (CTA). There is no standard definition of VAH; we defined it as a vertebral artery < 2 mm in diameter and the whole artery was slim or absent on CE-MRA or CTA. Univariate and multivariate logistic regression analyses were performed to identify significant independent risk factors for PCI stroke. RESULTS: There were 230 patients (27.3 %) diagnosed with PCI stroke and 91 patients diagnosed with VAH (10.8 %). Multivariate logistic regression analysis showed that VAH, male gender, and stenosis of the posterior circulation were independent risk factors for PCI stroke. CONCLUSIONS: Our results show that VAH is not rare in Chinese patients with stroke and that its presence increases the risk of PCI stroke.

Evaluation of cellulases produced from four fungi cultured on furfural residues and microcrystalline cellulose.

Four fungal strains-Trichoderma viride, Aspergillus niger, Trichoderma koningii, and Trichoderma reesei-were selected for cellulase production using furfural residues and microcrystalline cellulose (MCC) as the substrates. The filter paper activity (FPA) of the supernatant from each fungus was measured, and the performance of the enzymes from different fungal strains was compared. Moreover, the individual activities of the three components of the cellulase system, i.e., ß-glucosidase, endoglucanase, and exoglucanase were evaluated. T. koningii showed the highest activity (27.81 FPU/ml) on furfural residues, while T. viride showed an activity of 21.61 FPU/ml on MCC. The FPA of the crude enzyme supernatant from T. koningii was 30% higher on furfural residues than on MCC. T. koningii and T. viride exhibited high stability and productivity and were chosen for cellulases production. The crystallinity index (CrI) of the furfural residues varied after digested by the fungi. The results indicated differences in the functioning of the cellulase system from each fungus. In the case of T. koningii, T. reesei and T. viride, furfural residues supported a better environment for cellulase production than MCC. Moreover, the CrI of the furfural residues decreased, indicating that this material was largely digested by the fungi. Thus, our results suggest that it may be possible to use the cellulases produced from these fungi for the simultaneous saccharification and fermentation of lignocellulosic materials in ethanol production.

[Effects of telmisartan on the level of Aß1-42, interleukin-1ß, tumor necrosis factor α and cognition in hypertensive patients with Alzheimer's disease].

OBJECTIVE: To explore the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor γ-stimulating activity, on the levels of Aß1-42, interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and cognition in elderly hypertensive patients with Alzheimer's disease (AD). METHODS: A total of 48 patients with probable AD and essential hypertension were randomly assigned into telmisartan group (n = 24, 40 - 80 mg qd) or amlodipine group (n = 24, 5 - 10 mg qd) for 6 months at Henan Provincial People's Hospital during 2008 - 2011. Cognitive evaluations were assessed at pre-treatment and 24 weeks post-treatment by clinical assessment, rating scales and neuropsychological tests while the cerebrospinal fluid (CSF) levels of Aß1-42, IL-1ß and TNF-α by enzyme-linked immunosorbent assay (ELISA). RESULTS: After 6 months, mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) significantly decreased compared with baseline values to a similar extent in both groups. No significant differences existed between two groups in SBP or DBP. The patients displayed significantly higher Aß1-42 and greatly lower levels of IL-1ß and TNF-α in the telmisartan group versus the amlodipine group (P < 0.05). At 24 weeks, the patients in the telmisartan group had better mini-mental state examination (MMSE) (22.0 ± 3.4) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (15 ± 5) scales scores than those taking amlodipine (MMSE (19.5 ± 2.8) and ADAS-cog (18 ± 5). Patients treated with telmisartan had better improvement on the MMSE (P < 0.05) and ADAS-cog (P < 0.05) scales compared with the amlodipine group by the end of study week 24. CONCLUSION: Telmisartan may delay the decreased level of Aß1-42 and reduce the levels IL-1ß and TNF-α in CSF so as to improve the cognitive function of elderly hypertensive patients with AD. With additional benefits in comparison with common antihypertensive drugs, it may offer a novel therapeutic strategy of AD.

[Emulsion liquid membrane extraction with D2EHPA mobile carrier Hirudinaria manillensis hirudin in experimental study].

OBJECTIVE: To study the extraction system of hirudin emulsion liquid membrane with the Poecilobdella manillensis as raw material, di-(2-ethylhexyl) phosphate (D2EHPA) as carrier, Span 80 as emulsifier, octane and D2EHPA mixed to constitute membrane solution, diluted HCl solutions as internal aqueous phase. METHOD: Using the orthogonal experiment to optimize the extraction conditions of hirudin reference substance such as membrane phase, internal aqueous phase volume ratio (MIPVR), external aqueous phase pH, internal aqueous phase pH, mobile carrier concentration and so on, and then using hirudin crude extracts to do purifying experiment, and gaining experimental samples. RESULT: The optimal conditions of hirudin extraction were as follows: MIPVR 10: 3, internal aqueous phase pH 2.6, external aqueous phase pH 3.4, the mass fraction of carrier D2EHPA 2%. In the optimal extraction conditions, when the initial concentration of hirudin was one anti-thrombin activity units (ATU) x mL(-1), ATU recovery rate of the reference substance was 83.06%. In the purifying experiment of crude extracts, ATU recovery rate was 82.99%, and the specific activity of sample was 3 289.48 the ATU x mg(-1). Discontinuous polyacrylamide gel electrophoresis and spectral scanning, the results showed that the purity and reference substance were considerable. CONCLUSION: The method of preparation hirudin was relatively simple, the purity of the experimental samples and ATU recovery were both high.

Enzymatic degradation of steam-pretreated Lespedeza stalk (Lespedeza crytobotrya) by cellulosic-substrate induced cellulases.

The cellulase production by Trichoderma viride, cultivated on different substrates, namely steam-pretreated Lespedeza, filter paper, microcrystalline cellulose (MCC) or carboxymethyl cellulose (CMC), was studied. Different cellulase systems were secreted when cultivated on different substrates. The cellulolytic enzyme from steam-pretreated Lespedeza medium performed the highest filter paper activity, exoglucanase and endoglucanase activities, while the highest ß-glucosidase activity was obtained from the enzyme produced on filter paper medium. The hydrolytic potential of the enzymes produced from different media was evaluated on steam-pretreated Lespedeza. The cellulase from steam-pretreated Lespedeza was found to have the most efficient hydrolysis capability to this specific substrate. The molecular weights of the cellulases produced on steam-pretreated Lespedeza, filter paper and MCC media were 33, 37 and 40 kDa, respectively, and the cellulase from CMC medium had molecular weights of 20 and 43 kDa. The degree of polymerization, crystallinity index and micro structure scanned by the scanning electron microscopy of degraded steam-pretreated Lespedeza residues were also studied.

[Mouse stroke models and strains-related differences in susceptibility to cerebral ischemia].

Mouse stroke models provide experiment basis for study of the mechanisms of cell death and neural repair, and the neuroprotective effect of new drugs. There are at least three models of middle cerebral artery occlusion (MCAO) routinely used in experimental study. These models vary widely in their application in study of cell death or neural repair, and simulation of human diseases. This review article is focused on the characteristics of three mouse MCAO models and the strains-related differences in susceptibility to cerebral ischemia.

[Design and implementation of a VB-based virtual operation system for the console in an x-ray machine].

A new experimental software of an X-ray machine's console virtual operation system based on VB is introduced. This software can simulate the manual operation on the X-ray machine's console, and has the characteristics of easy operation, multi-function and good interactivity.

Lance-Adams syndrome: a report of two cases.

Chronic post-hypoxic myoclonus, also known as Lance-Adams syndrome (LAS), is a rare complication of successful cardiopulmanry resuscitation often accompanied by action myoclonus and cerebellar ataxia. It is seen in patients who have undergone a cardiorespiratory arrest, regained consciousness afterwards, and then developed myoclonus days or weeks after the event. Worldwide, 122 cases have been reported in the literature so far, including 1 case of Chinese. Here we report 2 Chinese LAS patients with detailed neuroimagings. Cranial single photon emission computed tomography (SPECT) of patient 1, a 52-year-old woman, showed a mild hypoperfusion in her left temporal lobe, whereas patient 2, a 54-year-old woman, manifested a mild bilateral decrease of glucose metabolism in the frontal lobes and a mild to moderate decrease of the N-acetyl aspartate (NAA) peak in the bilateral hippocampi by cranial [(18)F]-fluorodeoxyglucose positron emission tomographic (PET) scan and cranial magnetic resonance spectroscopy (MRS), respectively. We also review the literature on the neuroimaging, pathogenesis, and treatment of LAS.