Effect of Xixin decoction on phosphorylation toxicity at specific sites of tau protein in brains of rats with sporadic Alzheimer disease

AbstractObjectiveTo explore the mechanism of action of Xixin decoction (XXD) for the prevention and treatment of sporadic Alzheimer disease (SAD) by investigating the effects of XXD on the phosphorylation of Thr231 and Ser422 sites of tau protein.MethodsSpecific pathogen-free (SPF) male Sprague-Dawley (SD) rats with SAD were randomly divided into six groups: sham-operated, model (intracerebroventricular injection of Streptozotocin, ICV-STZ), donepezil (0.92 mg/kg), XXD low-dose (7.61 g/kg−1 · d−1), moderate-dose (15.21 g/kg−1 · d−1), and high-dose (30.42 g/kg−1 · d−1). Immunohistochemistry and western immunoblotting were used to detect the phosphorylation at Thr231 and Ser422 sites of tau protein.ResultsXXD different dose groups decreased to varying degrees the expression of phosphorylated tau at P-Thr231 and P-Ser422 sites in the hippocampus of SAD rats. No significant difference was found between the donepezil and model group.ConclusionXXD may prevent SAD pathological progress by inhibiting hyperphosphorylation at the key sites of tau proteins

Effect of Xixin decoction on O-linked N-acetylglucosamine Glycosylation of tau proteins in rat brain with sporadic Alzheimer disease

AbstractObjectiveTo study the effects of Xixin decoction (XXD) on O-linked N-acetylglucosamine (O-GlcNAc) glycosylation of tau proteins in rat brain with sporadic Alzheimer disease (SAD), and discuss its possible mechanism on prevention and treatment of SAD.MethodsThe rat model of SAD was established by intracerebroventricular injection of streptozotocin. The specific pathogen free male Sprague-Dawley rats were randomly divided into sham-operation group (S), model group (M), donepezil group (D), XXD at a low dose group (XL), XXD at a medium dose group (XM) and XXD at a high dose group (XH). After treatment and praxiology test, immunohistochemistry and western blotting were used to detect O-GlcNAc glycosylation level of tau proteins in rat brain with SAD. O-GlcNAc glycosylation and expression of tau proteins were detected by O-GlcNAc-specific antibodies RL2 and CTD110.6.ResultsO-GlcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significantly improved in the hippocampus of SAD rats. The differences were statistically significant among XXD groups (P<0.05, P<0.01), while no obvious differences were observed between D group and M group (P>0.05).ConclusionXXD can significantly improve O-GlcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hyperphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological process of SAD

Herbal therapy: a new pathway for the treatment of Alzheimer's disease

It has been a clinical challenge to treat Alzheimer's disease (AD). In the present commentary we discuss whether herbal therapy could be a novel treatment method for AD on the basis of results from clinical trials, and discuss the implications for potential therapy for AD pathophysiology. There is evidence to suggest that single herbs or herbal formulations may offer certain complementary cognitive benefits to the approved drugs. The current evidence supporting their use alone, however, is inconclusive or inadequate owing to many methodological limitations. Herbal mixtures may have advantages with multiple target regulation compared with the single-target antagonist in the view of traditional Chinese medicine. Several clinical trials using herbal mixtures are being conducted in China and will hopefully show promising results for treating AD in the near future

Systemic Revealing Pharmacological Signalling Pathway Networks in the Hippocampus of Ischaemia-Reperfusion Mice Treated with Baicalin

Background. Baicalin (BA) exhibits ill understood neuroprotective, anti-inflammatory, and antioxidative effects in brain injury. Objective. To identify the differential network pathways associated with BA-related biological effects. Methods. MCAO-induced mice received BA 5 mg/Kg (BA group). Controls received vehicle only. Following ischaemia-reperfusion, ArrayTrack analysed the whole genome microarray of hippocampal genes, and MetaCore analysed differentially expressed genes. Results. Four reversing pathways were common to BA and controls, but only 6 were in the top 10 for BA. Three of the top 5 signalling pathways in controls were not observed in BA. BA treatment made absent 3 pathways of the top 5 signalling pathways from the top 5 in controls. There were 2 reversing pathways between controls and BA that showed altered gene expression. Controls had 6 networks associated with cerebral ischaemia. After BA treatment, 9 networks were associated with cerebral ischaemia. Enrichment analysis identified 10 significant biological processes in BA and controls. Of the 10 most significant molecular functions, 7 were common to BA and controls, and only 3 occurred in BA. BA and controls had 7 significant cellular components. Conclusions. This study showed that the clinical effectiveness of BA was based on the complementary effects of multiple pathways and networks

Applicable conditions and analytical corrections of plane strain assumption in the simulation of hydraulic fracturing

Plane stain assumption is widely used in the simulation of the distribution of stress and displacement around hydraulic fractures. According to the comparison of the solutions of elliptical fracture and plane stain fracture, the applicable conditions of plane strain assumption were discussed and the correction method was put forward. On the basis of the past research, a classical stress and displacement solution around a flat elliptical fracture was deduced, fulfilled and corrected. In comparison with the plain strain fracture solution, simulating results show that if taking plane strain assumption into consideration in the fracture height profile, the difference between the elliptical fracture solution and plane strain solution is negligible when the ratio between fracture length and fracture height is larger than 10, and the above critical value could be relaxed to 5 in some simulations which normal stress perpendicular to fracture face plays a decisive role. The plane strain fracture solution is accurate enough when the above critical value is satisfied, the correction of the plane strain fracture solution is needed when the length-height ratio is small. The correction charts of the additional initial stress of the horizontal well with an open-hole and the width of a single fracture were drawn under different length-height ratios. The fracture width of pseudo three dimension propagation models is easier to be modified by the correction charts. Key words: hydraulic fracturing, plane strain, elliptical fracture, analytical model, correction char

Improved Stability Analysis for Neural Networks with Time-Varying Delay

This paper concerned the problem of delay-dependent asymptotic stability for neural networks with time-varying delay. A new class of Lyapunov functional dividing the interval delay is constructed to derive some new delay-dependent stability criteria. The obtained criteria are less conservative because free-weighting matrices method, a convex optimization approach, and a mixed dividing delay interval approach are considered. Finally, numerical examples are given to illustrate the effectiveness of the proposed method

The utility of the Hopkins Verbal Learning Test (Chinese version) for screening dementia and mild cognitive impairment in a Chinese population

Abstract Background The Hopkins Verbal Learning Test (HVLT) has been validated for detecting dementia in English-speaking populations. However, no studies have examined the Chinese version of the HVLT scale, and appropriate cut-off scores for dementia in the Chinese population remain unclear. Methods 631 subjects aged 60 and over were recruited at a memory clinic at Dongzhimen Hospital in Beijing. Of these, 249 were classified as exhibiting normal cognition (NC), 134 were diagnosed with mild cognitive impairment (MCI), 97 were diagnosed with Alzheimer’s disease (AD), 14 met the diagnosis for vascular dementia (VaD), and 50 were diagnosed with other types of dementia, including mixed dementia. The discriminative capacity of the HVLT total learning score, recognition score and total score were calculated to determine their sensitivity and specificity for detecting MCI, AD and other dementias, and various cut-off scores. Results HVLT scores were affected by age, education and sex. The HVLT total learning score exhibited an optimal balance between sensitivity and specificity using a cut-off score of 15.5 for distinguishing AD and other types of dementia from NC using the ROC curve, with sensitivity of 94.7% for distinguishing AD and all types of dementia, and specificity of 92.5% for detecting AD and 93.4% for detecting all types of dementias. We stratified the AD and MCI groups by age, and calculated the validity in each age group. In the 50–64 years age group, when the cutoff score was 18.5, the sensitivity of 0.955 and specificity of 0.921 were obtained for discriminating the NC and AD groups, and in the 65–80 years group, and optimal sensitivity and specificity values (0.948 and 0.925, respectively) were obtained with a cutoff score of 14.5. When the cutoff score was 21.5 in HVLT total recall, an optimal balance was obtained between sensitivity and specificity (69.1% and 70.7%, respectively) in distinguishing MCI from NC. Conclusion A cut-off score of 15.5 in the HVLT total learning score led to high discriminative capacity between the dementia and NC groups. This suggests that the HVLT total learning score can provide a useful tool for discriminating dementia, but not MCI, from NC in clinical and epidemiological practice.</p

Study on Corrosion Resistance and Conductivity of TiMoN Coatings with Different Mo Contents under Simulated PEMFC Cathode Environment

TiMoN coatings with different Mo contents on a SS316L substrate are deposited by using closed field unbalanced magnetron sputtering ion plating (CFUMSIP) technology to enhance the corrosion resistance and durability of stainless steel (SS) bipolar plates (BPs) in proton exchange membrane fuel cell (PEMFC) during the start-up/shut-down process. The electrochemical test results illustrate that TiMoN-4A coating has extremely good corrosion resistance compared to other coatings. The potentiostat polarization (+0.6 VSCE) tests indicate that the corrosion current density (Icorr) of TiMoN-4A coating is 5.22 &times; 10&minus;7A cm&minus;2, which meets the department of energy 2020 targets (DOE, &le;1 &times; 10&minus;6 A cm&minus;2). Otherwise, TiMoN-4A coating also exhibits the best corrosion resistance and stability in potentiostatic polarization, electrochemical impedance spectroscopy (EIS), and high potential (+1.2VSCE) polarization tests. The interfacial contact resistance (ICR) measurement results show that TiMoN-4A coating has the minimum ICR of 9.19 m&Omega;&middot;cm2, which meets the DOE 2020 targets (&le;10 m&Omega;&middot;cm2)