Search

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays several important roles in vasodilation, neurotransmission, neuromodulation and neurotrophy, as well as activation of the trigeminovascular system. The aim of the present study was to explore the relationship between altered PACAP levels in peripheral blood and different types of headache., Methods: The present study enrolled 101 outpatients with headache and 35 healthy control volunteers. Blood samples were collected from the cubital vein and peripheral blood mononuclear cells (PBMCs) were separated. Total mRNA in the PBMCs was extracted and the expression of PACAP mRNA was analyzed by quantitative-polymerase chain reaction (Q-PCR)., Results: There was a significant decrease in PACAP mRNA expression in the PBMCs of the migraine (M) group relative to the healthy control group. However, there were no significant differences in PACAP mRNA expression between the control group and tension-type headache (TTH), cluster headache (CH), or medication overuse headache (MOH) groups., Conclusion: The PBMC levels of patients with migraine, but not other commonly seen headache types, exhibited a significant reduction in PACAP mRNA expression compared with healthy control subjects.

γ-Secretase is one of two proteases directly involved in the production of the amyloid β-peptide (Aβ), which is pathogenic in Alzheimer's disease. Inhibition of γ-secretase to suppress the production of Aβ should not block processing of one of its alternative substrates, Notch1 receptors, as interference with Notch1 signaling leads to severe toxic effects. In the course of our studies to identify γ-secretase inhibitors with selectivity for APP over Notch, 1 [3-(benzyl(isopropyl)amino)-1-(naphthalen-2-yl)propan-1-one] was found to inhibit γ-secretase-mediated Aβ production without interfering with γ-secretase-mediated Notch processing in purified enzyme assays. As 1 is chemically unstable, efforts to increase the stability of this compound led to the identification of 2 [naphthalene-2-carboxylic acid benzyl-isopropyl-amide] which showed similar biological activity to compound 1. Synthesis and evaluation of a series of amide analogs resulted in benzofuranyl amide analogs that showed promising Notch-sparing γ-secretase inhibitory effects. This class of compounds may serve as a novel lead series for further study in the development of γ-secretase inhibitors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

One therapeutic approach for Alzheimer's disease is to inhibit the cleavage of the amyloid precursor protein (APP) by γ-secretase. At the beginning of a series of studies from our laboratories, a series of novel γ-amino alcohols (1) were found to possess γ-secretase inhibitory activity and Notch-sparing effects. A new one-pot synthesis of γ-amino alcohols and the structure-activity relationship (SAR) of these analogs will be discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A triboelectric sensor matrix (TESM) can accurately track and map 2D tactile sensing. A self-powered, high-resolution, pressure-sensitive, flexible and durable TESM with 16 × 16 pixels is fabricated for the fast detection of single-point and multi-point touching. Using cross-locating technology, a cross-type TESM with 32 × 20 pixels is developed for more rapid tactile mapping, which significantly reduces the addressing lines from m × n to m + n., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Biological and pharmacological activities of dryocrassin ABBA, a phloroglucinol derivative extracted from Dryopteris crassirhizoma, have attracted attention. In this study, the apoptotic effect of dryocrassin ABBA on human hepatocellular carcinoma HepG2 cells was investigated., Materials and Methods: We tested the effects of dryocrassin ABBA on HepG2 in vitro by MTT, flow cytometry, real-time PCR, and Western blotting. KM male mice were used to detect the effect of dryocrassin ABBA on H22 cells in vivo., Results: Dryocrassin ABBA inhibited the growth of HepG2 cells in a concentration-dependent manner. After treatment with 25, 50, and 75 μg/mL dryocrassin ABBA, the cell viability was 68%, 60% and 49%, respectively. Dryocrassin ABBA was able to induce apoptosis, measured by propidium iodide (PI)/annexin V-FITC double staining. The results of real-time PCR and Western ting showed that dryocrassin ABBA up-regulated p53 and Bax expression and inhibited Bcl-2 expression which led to an activation of caspase-3 and caspase-7 in the cytosol, and then induction of cell apoptosis. In vivo experiments also showed that dryocrassin ABBA treatment significantly suppressed tumor growth, without major side effects., Conclusions: Overall, these findings provide evidence that dryocrassin ABBA may induce apoptosis in human hepatocellular carcinoma cells through a caspase-mediated mitochondrial pathway.

A large array of Schottky UV photodetectors (PDs) based on vertical aligned ZnO nanowires is achieved. By introducing the piezo-phototronic effect, the performance of the PD array is enhanced up to seven times in photoreponsivity, six times in sensitivity, and 2.8 times in detection limit. The UV PD array may have applications in optoelectronic systems, adaptive optical computing, and communication., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) is associated with migraine phase; however, whether PACAP levels could be used to distinguish between migraine and tension-type headache (TTH) remains unknown. We compared interictal plasma PACAP levels among healthy controls, migraineurs, and patients with TTH., Methods: Interictal plasma levels of PACAP were measured in 133 migraineurs, 106 patients with TTH, and 50 controls using enzyme-linked immunoassays. We further evaluated the relationships between interictal PACAP plasma concentrations and clinical parameters, such as headache severity, attack frequency, and duration., Results: We found that migraineurs had significantly lower interictal plasma PACAP levels than patients with TTH and healthy controls. However, there were no significant differences between patients with TTH and healthy controls. Plasma PACAP levels were significantly lower in patients with episodic migraine (EM) than in patients with episodic tension-type headache (ETTH) and in patients with chronic migraine (CM) than in patients with chronic tension-type headache (CTTH). Interictal PACAP levels were negatively correlated with duration in the CM group., Conclusions: The results of this study demonstrated differences in interictal PACAP levels in migraine and TTH, suggesting that PACAP is involved in the pathogenesis of migraine rather than TTH., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, while previous studies point to a pivotal role of neuroinflammation in the pathophysiology of PD. As a member of pattern recognition receptors, TLR4 plays an important role in the immune response and inflammatory responses. Growing evidences suggest that mutation of TLR4 gene may be connected with the development of PD. The objective of this study was to evaluate whether genetic polymorphisms of the TLR4 gene are associated with PD susceptibility. We genotyped three single-nucleotide polymorphisms of the TLR4 gene (rs1927911, rs1927914 and rs10116253) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in unrelated 380 PD patients and 380 healthy-matched controls. Our study revealed that rs1927914 C allele carriers and C allele were probably related to a decreased risk of PD (p = 0.032 and p = 0.028, respectively) as well as male PD (p = 0.034) and early-onset PD (EOPD) (p = 0.023). In addition, there were significant differences in genotype and allele distribution in male PD patients and its healthy-matched control subgroup (p = 0.035 and p = 0.012, respectively). For rs1927911 and rs10116253 polymorphisms, genotype or allele frequencies did not differ between groups. Our data suggest that the TLR4 gene might contribute to the risk of developing PD in Han Chinese and rs1927914 polymorphism may be a protective factor for sporadic PD, male PD and EOPD.

Spiroacetals can be formed through a one-pot sequence of a hetero-Diels-Alder reaction, an oxidative carbon-hydrogen bond cleavage, and an acid treatment. This convergent approach expedites access to a complex molecular subunit which is present in numerous biologically active structures. The utility of the protocol is demonstrated through its application to a brief synthesis of the actin-binding cytotoxin bistramide A., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Previous studies have indicated that genetic polymorphisms in the P2X7 receptors may influence the occurrence and development of sporadic Parkinson's diseases (PD). In our study, two DNA polymorphisms at P2X7 receptor gene: 1513A>C (rs3751143) and 1729T>A (rs1653624) were examined by PCR-RFLP analysis in 285 sporadic patients and 285 healthy controls in Han Chinese population. For 1513A>C polymorphism, there were significant differences in genotype distribution in PD group and late-onset PD (LOPD) group relative to the control groups respectively (P=0.015 and P=0.032, respectively), as well as between male PD and the controls subgroup (P=0.031). However, there were no significant differences in the genotype and allele frequencies of 1729T>A polymorphism between groups. Our study revealed that the P2X7 receptors 1513A>C polymorphism is a risk factor for sporadic PD, LOPD and male PD in Han Chinese population, while 1729T>A polymorphism is not significantly associated with Parkinson's disease., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Vitamin D receptor (VDR) has been proposed as a candidate gene for susceptibility to Parkinson's disease (PD). This study was set to assess the association between VDR gene Apa I and Taq I polymorphisms and PD in a Chinese Han population., Methods: Two hundred and eighty five sporadic PD patients and 285 healthy controls were genotyped for the Apa I and Taq I polymorphisms in VDR gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: No significant difference was detected in genotype or allele distribution of both Apa I and Taq I polymorphisms between PD patients and controls (P U+003E 0.05). No TT genotype for Taq I was found in the studied population. For Taq I, the distribution of genotype was significantly different between male PD patients and controls (U+03C7 2=4.187, P=0.032, OR=2.149, 95%CI: 1.011-4.567), and the frequency of T allele was significantly higher in male PD patients than male controls (U+03C7 2=3.867, P=0.036, OR=2.064, 95%CI: 0.989-4.307)., Conclusion: VDR gene Apa I polymorphisms are not associated with sporadic Parkinson's disease, but Taq I may be a risk factor for male PD.

Vitamin D plays an important role in neurodegenerative disorders as a crucial neuro-immunomodulator, and accumulating data have provided evidence for that vitamin D receptor (VDR) gene is a candidate gene for susceptibility to Parkinson's disease (PD). In this study, we performed a case-control study to demonstrate whether the risk for the development of onset of sporadic PD might be influenced by VDR gene polymorphisms in a Chinese cohort. Two hundred and sixty PD patients and 282 matched-healthy controls were genotyped for two representative single nucleotide polymorphisms (SNPs) in VDR gene (FokI C/T and BsmI G/A) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis in. Results from our study revealed that FokI C allele carriers were likely to associate with an increased risk of PD (P=0.004) as well as early-onset PD (EOPD) (P=0.010). Moreover, the frequency of FokI C allele was significantly increased in PD group and late-onset PD (LOPD) group relative to the control groups respectively (P=0.023 and P=0.033, respectively). For BsmI polymorphisms, no significant difference in genotype or allele distribution was found between PD patients and the controls, as well as gender- and age-related differences between PD patients and the controls subgroup. This study demonstrated a possible association between the VDR FokI T/C polymorphism and PD, indicating that VDR polymorphisms may well change genetic susceptibility to sporadic PD in a Han Chinese population., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

[Structure: see text] A practical one-pot, regiospecific three-component process for the synthesis of 2,3-disubstituted indoles was developed via consecutive Pd-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.

A novel generation of 1-iodo-3-siloxy-1,3-butadienes has been developed by reacting trimethylsilyl iodide (TMS-I) with alpha, beta-unsaturated ketones in dichloromethane at 0 degrees C without the use of any catalyst. The halo aldol reaction of these butadiene intermediates with aldehydes was efficiently carried out by using magnesium iodide as the catalyst. Twelve beta-iodo-alpha,beta-unsaturated-beta'-hydroxyketones (halo aldols) have been synthesized under the new condition with excellent geometric selectivity and good chemical yields (>80% chemical yields for 11 examples).

N,N-dichloro-o-nitrobenzenesulfonamide (2-NsNCl2) was found to be an effective electrophilic nitrogen source for the direct diamination of alpha,beta-unsaturated ketones without the use of any metal catalysts. The reaction is very convenient to carry out without the protection of inert gases. Molecular sieves (4 A) and temperature were found to play key roles in controlling the formations of 3-trichloromethyl and dichloromethyl imidazoline products (16 examples). The 2-Ns-protection group of the resulting diamine products can be easily cleaved under mild Fukuyama's conditions. A new mechanism hypothesis of [2+3] cyclization and N-chlorination has been proposed to explain the product structures, particularly their regio- and stereochemistry.

alpha,beta-Differentiated 1,2-vicinal diamines have been efficiently synthesized by using new electrophilic imidazolination reaction of alkenes. The hydrolysis of imidazolines was performed by treatment with 6 M HCl in THF at 70 degrees C without epimerization. Eight examples were examined to give good to excellent yields (87-96%).

A new direct electrophilic diamination reaction of alpha,beta-unsaturated ketones and esters has been established without the use of any metal catalysts. Three types of nitriles (CH(3)CN, CH(3)CH(2)CN, and CH(3)CH(2)CH(2)CN) were employed as nucleophilic nitrogen sources. A new mechanism has also been proposed to explain the resulting regio- and stereoselectivity.

A new asymmetric approach to chiral beta-iodo Baylis-Hillman hydroxy esters was developed via a tandem asymmetric I-C/C-C formation reaction. The reaction was conveniently carried out by slow addition of diethylaluminum iodide into a mixture of aldehyde and alpha,beta-acetylenic menthyl ester in dichloromethane at -23 degrees C. Excellent geometric selectivity, promising diastereoselectivity and modest to high yields (up to 91%) were obtained., (Copyright 2003 Wiley-Liss, Inc.)

The Baylis-Hillman condensation of three types of alpha,beta-conjugate cycloketones with aldehydes was successfully performed by using diethylaluminum iodide as the Lewis acid promoter alone without the direct use of a Lewis base. The reaction proceeded to completion at 0 degree C in CH2Cl2 within 24 h to give modest to good yields (53-72%).

The Baylis-Hillman-type reaction of alpha,Beta-ethyl thioacrylate with aldehydes has been achieved using diethylaluminium iodide as the promoter without the direct use of any Lewis bases. The reaction provides an effective access to various alpha-methylene-Beta-hydroxy thioesters.

The FeCl(3)-PPh(3) complex was found to effectively catalyze the electrophilic diamination reaction of electron-deficient alkenes. Improvements on yields and stereoselectivity have been achieved for both alpha,beta-unsaturated carboxylic esters and ketones. Under the new catalytic system, alpha,beta-unsaturated carboxylic esters were found to be superior to their ketone counterparts, which is opposite to the previous (C(3)F(7)CO(2))(2)Rh](2)-catalyzed diamination. The reaction employs readily available N,N-dichloro-p-toluenesulfonamide (TsNCl(2)) and acetonitrile as the nitrogen sources and is very easy to perform at room temperature without the special protection of inert gases. The resulting diamino products belong to imidazolidine analogue and can further strengthen the importance of the new reaction. Modest to good yields (52-84%) and high regio- and stereoselectivity have been achieved for 10 examples.