This study aimed to investigate the independent and interactive influences of apolipoprotein E (APOE) epsilon4 and beta-amyloid (Abeta) on multiple cognitive domains in a large group of cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants were included if clinical and cognitive assessments, amyloid imaging, and APOE genotype were all available from the Alzheimer's Disease Neuroimaging Initiative database (CN = 324, MCI = 502, AD = 182). Individuals with one or two copies of epsilon4 were designated as APOE epsilon4 carriers (epsilon4+); individuals with no epsilon4 were designated as APOE epsilon4 non-carriers (epsilon4-). Based on mean florbetapir standard uptake value ratios, participants were classified as Abeta burden-positive (Abeta+) or Abeta burden-negative (Abeta-). In MCI, APOE epsilon4 effects were predominantly observed on frontal executive function, with epsilon4+ participants exhibiting poorer performances; Abeta positivity had no influence on this effect. Abeta effects were observed on global cognition, memory, and visuospatial ability, with Abeta+ participants exhibiting poorer performances. Measures of frontal executive function were not influenced by Abeta. Interactive effects of APOE epsilon4+ and Abeta were observed on global cognition and verbal recognition memory. Abeta, not APOE epsilon4+, influenced clinical severity and functional status. The influences of APOE epsilon4+ and Abeta on cognitive function were minimal in CN and AD. In conclusion, we provide further evidence of both independent and interactive influences of APOE epsilon4+ and Abeta on cognitive function in MCI, with APOE epsilon4+ and Abeta showing dissociable effects on executive and non-executive functions, respectively.
Aged ; Aged, 80 and over ; Alzheimer Disease/genetics/pathology ; Amyloid beta-Peptides/*metabolism ; Aniline Compounds/chemistry ; Apolipoprotein E4/*genetics ; Brain/radiography ; Cognition ; Databases, Factual ; Demography ; Ethylene Glycols/chemistry ; Female ; Genotype ; Humans ; Male ; Mild Cognitive Impairment/genetics/*pathology ; Positron-Emission Tomography

We prepared protoplasts from Salvia miltiorrhiza Bunge suspension culture cells. Then, the protoplasts' vitality and functions were tested by fluorescein diacetate staining method and Fluo-3/AM flourescent probe. The optimal condition of protoplast isolation was Cellulase R-10 1.5%, Pectinase Y-23 0.3%, Macerozyme R-10 0.5%, 40 r/min 12 h, 600 r/min 5 min, and the protoplasts yield was 1.1x10(6) cells/g FW, the vitality was more than 95% by using fluorescein diacetate staining method. It has been confirmed that calcium fluorescent probe Fluo-3/AM can be successfully loaded into protoplasts.
Aniline Compounds ; chemistry ; Cell Culture Techniques ; Cellulase ; chemistry ; Fluorescent Dyes ; chemistry ; Protoplasts ; chemistry ; Salvia miltiorrhiza ; growth & development ; Xanthenes ; chemistry

The metabolite profiling of DAPA-7012 and DAAN-4442, the lead compounds from two new kinds of non-nucleoside reverse transcriptase inhibitors (NNRTIs), was performed using an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), with the assistance of a metabolite data processing software. By utilizing the mass defect filter (MDF) technique, the data acquired from the 0 h-incubation and the 2 h-incubation were compared and analyzed with the MetaboLynx software. After incubation, 14 metabolites of DAPA-7012 and 14 metabolites of DAAN-4442 were found in rat liver microsome. The MS2 spectra for some metabolites were obtained using the MS(E) technique to get fragment ions for structural elucidation. The results indicated that both compounds could undergo extensive metabolism in rat liver microsomes. The major phase I reaction was oxidation/hydroxylation. The major phase II reaction was S-glutathione conjugation. The metabolic pathways were similar between the two lead compounds, though they have different backbone structures. Besides, the 4-NO2 of ring B in DAAN-4442 was susceptible to reduction, the benzyl of ring C in DAPA-7012 was tend to be oxidized. The common metabolic soft spots were primary amine of ring B and two methyl groups of ring C. Early SAR results showed that the primary amine and methyl were necessary substituent groups. The stability of these active groups needs to be improved and optimized. The approach of combining metabolites information and structure-activity analysis can provide a reference for further structural optimization.
Aniline Compounds ; chemistry ; metabolism ; Animals ; Anti-HIV Agents ; chemistry ; metabolism ; Chromatography, High Pressure Liquid ; Microsomes, Liver ; metabolism ; Molecular Structure ; Pyridines ; chemistry ; metabolism ; Rats ; Reverse Transcriptase Inhibitors ; chemistry ; metabolism ; Spectrometry, Mass, Electrospray Ionization

The discovery of high performance leading antidiabetic compounds containing sulfonamide and 4-aminophenylacetic acid moieties is reported. This was achieved by the synthesis of 6 intermediates and subsequently 20 target molecules using 4-aminophenylacetic acid as the starting materials, and through a few synthetic routes aided by multi-step reactions including sulfonylation of amino group, deacylation of amides and esterification of carboxyl group, as well as acylation of amino group. The chemical structures of the twenty-four new compounds were determined using 1H NMR, 13C NMR and HR-MS techniques. Screening in vitro of their peroxisome proliferator-activated receptor (PPAR) activation activities showed weak relative PPAR activation activities to most of the target molecules. However, 4 target molecules exhibit PPAR over 58%, and as high as 81.79% for TM2-i, presenting itself as potent leading compound for antidiabetic drugs. This research also confirms that it is probable to achieve esterification of carboxyl group and deacylation of fatty acid N-phenyl amides concurrently in SOCl2/alcohol solvent system. This provides new synthetic method for the selective reaction within molecules containing both carboxyl and N-aryl amido groups of fatty acids.
Aniline Compounds ; chemistry ; Fatty Acids ; chemistry ; Hep G2 Cells ; metabolism ; Humans ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Phenylacetates ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Sulfonamides ; chemistry

Alzheimer's disease (AD) is a progressive neurodegenerative disease endangering human health seriously. Recent reports have revealed that beta-amyloid aggregates play a key role in the pathogenesis of AD. Thus, targeting the Abeta plaques benzothiazole derivatives were synthesized with the scaffold of the most promising imaging agent PIB ([11C]-6-OH-BTA-1, [11C]-2-(4-(methylamino)phenyl)-6-hydroxybenzothiazole) and C = N as linker to study the binding characteristics with the target protein through surface plasmon resonance (SPR) technique. These derivatives were synthesized through simple yet effective method with high yields and characterized by 1H NMR and FTIR. The binding properties (K(D)) were determined with Biacore X-100 instrument according to the fitting-plot curve. Compounds 3a and 3f showed high binding affinity for Abeta1-40. The results suggest that benzothiazole derivatives could be served as a scaffold to develop novel beta-amyloid imaging agents for the diagnosis of AD.
Alzheimer Disease ; diagnosis ; Amyloid beta-Peptides ; chemistry ; Aniline Compounds ; chemistry ; Benzothiazoles ; chemical synthesis ; chemistry ; Humans ; Peptide Fragments ; chemistry ; Protein Binding ; Schiff Bases ; chemical synthesis ; chemistry ; Surface Plasmon Resonance ; Thiazoles ; chemistry

Photoreactive heparin was synthesized by reaction of 4-azidoaniline and heparin. An organic layer was introduced on the surface of Ti-O by 3-aminopropylphosphonic acid assembling, and then the modified heparin was immobilized on the surface by UV irradiation. Water contact angle was used to characterize the hydrophilicity, quantitive assay was done by azure staining methods, and blood compatibility was evaluated by platelet adhesion experiment. Water contact angle of heparinized surface was smaller than that of Ti-O film, which indicated more hydrophilic property of heparinized surface. The surface density of heparin increased with the prolonging of irradiation time and the density was 2.1 microg/cm2 when irradiated for 300s. It showed the heparinized surface was effective in resisting platelets from adhesion and aggregation.
Aniline Compounds ; chemistry ; Azo Compounds ; chemistry ; Blood Proteins ; pharmacology ; Fibrinolytic Agents ; pharmacology ; Heparin ; chemistry ; Humans ; Membranes, Artificial ; Propylamines ; chemistry ; Surface Properties ; Titanium ; chemistry

Mammalian oocyte maturation and early embryo development processes are Ca(2+)-dependent. In this study, we used confocal microscopy to investigate the distribution pattern of Ca2+ and its dynamic changes in the processes of bovine oocytes maturation, in vitro fertilization (IVF), parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT) embryo development. During the germinal vesicle (GV) and GV breakdown stage, Ca2+ was distributed in the cortical ooplasm and throughout the oocytes from the MI to MII stage. In IVF embryos, Ca2+ was distributed in the cortical ooplasm before the formation of the pronucleus. In 4-8 cell embryos and morulas, Ca2+ was present throughout the blastomere. In PA embryos, Ca2+ was distributed throughout the blastomere at 48 h, similar to in the 4-cell and 8-cell phase and the morula. At 6 h after activation, there was almost no distribution of Ca2+ in the SCNT embryos. However, Ca2+ was distributed in the donor nucleus at 10 h and it was distributed throughout the blastomere in the 2-8 cell embryos. In this study, Ca2+ showed significant fluctuations with regularity of IVF and SCNT groups, but PA did not. Systematic investigation of the Ca2+ location and distribution changes during oocyte maturation and early embryo development processes should facilitate a better understanding of the mechanisms involved in oocyte maturation, reconstructed embryo activation and development, ultimately improving the reconstructed embryo development rate.
Aniline Compounds/chemistry ; Animals ; Calcium/*physiology ; Cattle/*physiology ; Embryonic Development/*physiology ; Female ; Fertilization in Vitro/*veterinary ; Microscopy, Confocal/veterinary ; Oocytes/*physiology ; Parthenogenesis/*physiology ; Xanthenes/chemistry

OBJECTIVENitrobenzene extraction enhanced by salting-out effect was employed to recover aniline from wastewater at 25 degrees C.

METHODBatchwise experiments were conducted to elucidate the influence of various operating variables on the extracting performance, including acidity of wastewater, initial aniline concentration, ratios of solvent to wastewater, extraction stages, concentrations and different types of inorganic salts, such as NaCl, KCl, Na(2)SO(4), CaCl(2) and K(2)SO(4).

RESULTSNitrobenzene with a concentration of 20% and a pH value of 9.1 at the temperature of 25 degrees C together with NaCl of a concentration of 14 wt.% realized nearly 100% aniline recovery at the fifth stage of wastewater treatment.

CONCLUSIONSHigh pH values and volume ratios of nitrobenzene/wastewater are more suitable for recovery of aniline. In addition, recovery of aniline is significantly elevated with increase of the concentration of salts, whose promoting effects are in the following order: NaCl>Na(2)SO(4)>K(2)SO(4)>CaCl(2)>KCl on the weight basis of wastewater. Furthermore, aniline in wastewater can be almost completely recovered by five-stage sequential nitrobenzene extraction, which is promoted continuously by the salting-out effect.

A series of N-(3-cyano-6-methyl-4-anilinoquinoline-7-yl) amide derivatives 13a-13n have been synthesized, their structures were confirmed with 1H NMR, EI-MS, IR and elemental analysis. Antitumor activities of all the synthesized compounds in vitro were tested with MTT. Compound 13j showed better than or equal antitumor activity on Bosutinib and EKB-569.
Aniline Compounds ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Humans ; Quinolines ; chemical synthesis ; chemistry ; pharmacology

Because c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 33 inhibited both enzymes with the IC50 values of 0.0484 micromol x L(-1) and 34.5 micromol x (-1), respectively. Some of the compounds also showed moderate anti-proliferation activities at 10 micromol x L(-1) against colon cancer HT-29 and liver cancer HepG2 cell lines.
Aniline Compounds ; chemical synthesis ; chemistry ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Delivery Systems ; Drug Design ; Humans ; Nitric Oxide Synthase Type II ; antagonists & inhibitors ; metabolism ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; metabolism ; Quinolines ; chemical synthesis ; chemistry ; pharmacology ; src-Family Kinases