Inhibitory Effect of N-Acyl Dopamines on IgE-Mediated Allergic Response in RBL-2H3 Cells

Recently, endogenous N-acyl dopamines have been found to show anti-inflammatory and immunomodulatory activities. However, the effect of the N-acyl dopamines on allergic responses was not reported. In this study, we investigated whether N-acyl dopamines might inhibit immunoglobulin E-mediated degranulation in RBL-2H3 cells. When RBL-2H3 cells were exposed to palmitoyl dopamine (NP-DA), oleoyl dopamine (NO-DA) or arachidonoyl dopamine (NA-DA) at micromolar levels, all these compounds significantly inhibited the release of β-hexosaminidase, a marker of degranulation, as well as tumor necrosis factor (TNF)-α. In comparison, NP-DA, potently suppressing the release of β-hexosaminidase (IC₅₀, 3.5 μM) and TNF-α (IC₅₀, 2.2 μM), was more potent than NO-DA or NA-DA. Additionally, NP-DA markedly suppressed the formation of prostaglandin E₂, prostaglandin D₂ and leukotriene C₄, corresponding to pro-inflammatory lipid mediators in asthma. In the mechanistic analyses, where the effect of NP-DA on the FcεRI cascade was examined, NP-DA significantly inhibited the phosphorylation and expression of Syk, but not Lyn. And, NP-DA also suppressed phosphorylation of ERK1/2 and Akt. Further, NP-DA decreased the phosphorylation of cPLA₂ and 5-lipoxygenase (5-LO), but not cyclooxygenase-2 (COX-2). Based on these results, it is suggested that NP-DA exert anti-allergic effect on allergic response through suppressing the activation of Syk, ERK1/2, Akt, cPLA₂ and 5-LO. Besides, a strong inhibition of COX-2 activity by NP-DA may be additional mechanism for its anti-allergic action. Such an anti-allergic action of N-acyl dopamines may contribute to further information about biological functions of N-acyl dopamines.     

Hyrtiosal, from the marine sponge Hyrtios erectus, inhibits HIV-1 integrase binding to viral DNA by a new inhibitor binding site

HIV-1 integrase (IN) is composed of three domains, the N-terminal domain (NTD, residues 1-50), the catalytic core domain (CCD, residues 51-212), and the C-terminal domain (CTD, residues 213-288). All the three domains are required for the two known integration reactions. CCD contains the catalytic triad and is believed to bind viral DNA specifically, and CTD binds viral DNA in a nonspecific manner. As no clear evidence has confirmed the involvement of NTD in DNA binding directly, NTD has not been seriously considered and less is known about its function in viral replication. In the current work, using a SPR technology-based assay, the HIV-1 viral DNA was determined to bind directly to NTD with a K(D) value of 8.8 microM, suggesting that the process of preintegrated complex formation for HIV-1 IN might involve the direct interaction of NTD with viral DNA in addition to binding of viral DNA to the catalytic core domain and C-terminal domain. Moreover, such viral DNA/IN binding could be inhibited by the marine product hyrtiosal from the marine sponge Hyrtios erectus with an IC(50) of 9.60+/-0.86 microM. Molecular dynamic analysis correlated with a site-directed mutagenesis approach further revealed that such hyrtiosal-induced viral DNA/IN binding inhibition was caused by the fact that hyrtiosal could bind HIV-1 NTD at Ser17, Trp19, and Lys34. As hyrtiosal was recently discovered by us as a protein tyrosine phosphatase 1B (PTP1B) inhibitor,1 this work might also supply multiple-target information for this marine product, and the verified HIV-NTD/HIV-1 IN interaction model could have further implications for new HIV-1 IN inhibitor design and evaluation.     

New Perspectives on the Gas–Solid Reaction of α‐Si3N4 Powder in Wet Air at High Temperature

The reaction behavior of chemically vapor‐deposited silicon nitride (α‐Si₃N₄) powder in wet air at 1673–1873 K for 10 h has been investigated. The oxidation and volatilization reaction coexist initially while volatilization reaction progressively becomes the limiting step with extended reaction time. Based on the experimental curves, a new kinetic model regarding both solid product layer and hypothetically volatile product layer has been developed to interpret its short‐term reaction and predict long‐term corrosion behavior. The calculated results agree well with the experimental data. Predictably, this new kinetic model can not only be used to treat the reaction of Si₃N₄ powder in wet air but also can be applied to deal with the gas–solid reaction of other ceramic powders.     

p110Delta Inhibits Monocyte Infiltration by Thioglycollate‐Induced Periotoneal Inflammation but Not HCD‐Induced Inflammation and Atherosclerosis in APOE KO Mice

We have previously reported that phosphoinositide 3‐kinase p110δ knockout (p110δ KO) diminished the adhesion of leukocytes to capillary venules and suppressed the peritoneal infiltration of leukocytes, both functions that play important roles in atherosclerosis. Therefore, we hypothesized that p110δ deficiency might be protective against atherosclerosis. Apolipoprotein E knockout (ApoE KO) mice were crossed with p110δ KO mice to generate homozygous double knockout mice (ApoE/p110δ DKO). The present study showed that ApoE/p110δ DKO mice fed with a high cholesterol diet (HCD) demonstrated less peritoneal infiltration of leukocytes and monocytes compared with ApoE KO mice after intraperitoneal injection of thioglycollate, an inducer of acute peritoneal inflammation. Unexpectedly, atherosclerosis in the aortic root and in the entire aorta was similar between the ApoE/p110δ DKO and ApoE KO groups. No difference in Mac‐3 expression, indicative of macrophage infiltration, was found between the two groups. Further analysis showed that ApoE KO mice chronically fed with HCD had increased levels of total cholesterol, low‐density lipoprotein in the blood and counts and percentages of circulating monocytes compared with ApoE KO mice fed with a normal diet. Consistently, the deficiency of p110δ affected neither the counts nor the percentages of monocytes nor the lipid profiles in the blood. The results suggested that p110δ plays an important role in acute but not in chronic inflammation, the latter being included in the early characteristics of atherosclerosis, which might explain the finding that p110δ deficiency fails to inhibit early atherosclerosis.     

Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion

Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)‐3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n‐3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi‐purified diets (20 % w/w fat) containing high n‐3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n‐3 PUFA (10 % w/w), medium n‐3 PUFA (4 % w/w), or low n‐3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase‐2 (DGAT‐2), fatty acid binding protein‐4 (FABP‐4) and leptin were measured. The high n‐3 PUFA group showed higher levels of total n‐3 PUFA in gonadal TAG compared to the medium and low n‐3 PUFA groups (P < 0.001). The high n‐3 PUFA male group had a lower adipocyte area compared to the medium and low n‐3 PUFA group (P < 0.001); however, no difference was observed in females. The high n‐3 PUFA male group showed lower mRNA expression of FABP‐4, DGAT‐2 and leptin compared to the low n‐3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n‐3 PUFA group compared to the other groups. Our findings show for the first time that n‐3 PUFA prevents adipocyte hypertrophy by downregulating FABP‐4, DGAT‐2 and leptin; the effects are however sex‐specific.     

Enantioselective N‐Heterocyclic Carbene‐Catalyzed [3+3] Annulation of α,β‐Unsaturated Esters with Methyl Ketoimine

Herein, we disclose the N‐heterocyclic carbene (NHC)‐catalyzed [3+3] annulation of challenging esters with methyl ketoimines for the highly enantioselective synthesis of intriguing δ‐lactams featuring various substituent patterns. The annulation occurs under mild conditions and offers good tolerance, good yields and excellent enantioselectivities. The six‐membered heterocyclic products are valuable for the synthesis of bioactive molecules.

     

Design,Synthesis, and Characterization of a Photoactivatable Caged Prodrug of Imatinib

Imatinib is the first protein kinase inhibitor approved for clinical use and is a seminal drug for the concept of targeted therapy. Herein we report on the design, synthesis, photokinetic properties, and in vitro enzymatic evaluation of a photoactivatable caged prodrug of imatinib. This approach allows spatial and temporal control over the activation of imatinib triggered by ultraviolet light. The successful application of the photoactivation concept to this significant kinase inhibitor provides further evidence for the caging technique as a feasible approach in the kinase field. The presented photoactivatable imatinib prodrug will be highly useful as a pharmacological tool to study the impact of imatinib toward biological systems in greater detail.     

Effects of culture pH on the production of bioactive polysaccharides by Agaricus blazei in batch cultures

The effects of culture pH on the production, molecular weight distribution and the bioactivity of polysaccharides produced by Agaricus blazei were evaluated by four pH‐controlled batch cultures. As the culture pH of each batch was controlled from 4.0 to 7.0, the maximum polysaccharide concentration increased from 561 to 1252 mg dm^?3, but the average molecular weight of the polysaccharides decreased monotonically from 1080 kDa to 600 kDa, the relative amount of β‐glucan from 56% to 33%, and the TNF‐α release by macrophage cells from 1440 to 760 pg per 5 × 10⁴ cells. Polysaccharides with higher molecular weights, β‐glucan contents and bioactivities were obtained in the submerged cultures of Agaricus blazei at lower culture pH but with lower yields. Copyright © 2004 Society of Chemical Industry     

Homogeneous graft copolymerization of chitosan with butyl acrylate by γ‐irradiation via a 6‐O‐maleoyl‐N‐phthaloyl‐chitosan intermediate

The graft copolymerization of butyl acrylate (BA) onto chitosan was tried via a new protection‐graft‐deprotection procedure. About 6‐O‐maleoyl‐N‐phthaloyl‐chitosan was synthesized and characterized by Fourier transform infrared spectra analysis (FT‐IR) and ¹H‐NMR. Because the intermediate 6‐O‐maleoyl‐N‐phthaloyl‐chitosan was soluble in organic solvents, the graft copolymerization was carried out in a homogeneous system. Grafting was initiated by γ‐irradiation. The graft extent was dependent on the irradiation dose and the concentration of BA monomer, and copolymers with grafting above 100% were readily prepared. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 489–493, 2006     

Study of jute fiber reinforced polyester composites by dynamic mechanical analysis

Cyanoethylation of jute fibers in the form of nonwoven fabric was studied, and these chemically modified fibers were used to make jute–polyester composites. The dynamic mechanical thermal properties of unsaturated polyester resin (cured) and composites of unmodified and chemically modified jute–polyester were studied by using a dynamic mechanical analyzer over a wide temperature range. The data suggest that the storage modulus and thermal transition temperature of the composites increased enormously due to cyanoethylation of fiber. An increase of the storage modulus of composites, prepared from chemically modified fiber, indicates its higher stiffness as compared to a composite prepared from unmodified fiber. It is also observed that incorporation of jute fiber (both unmodified and modified) with the unsaturated resin reduced the tan δ peak height remarkably. Composites prepared from cyanoethylated jute show better creep resistance at comparatively lower temperatures. On the contrary, a reversed phenomenon is observed at higher temperatures (120°C and above). Scanning electron micrographs of tensile fracture surfaces of unmodified and modified jute–polyester composites clearly demonstrate better fiber–matrix bonding in the case of the latter. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1505–1513, 1999     

Enantioselective Synthesis of cis‐4‐Formyl‐β‐lactams via Chiral N‐Heterocyclic Carbene‐Catalyzed Kinetic Resolution

An efficient synthesis of optically pure cis‐4‐formyl‐β‐lactams (up to 99% ee) by a chiral NHC‐catalyzed ring expansion reaction has been realized, featuring the ready availability of both the substrate and the catalyst, and the mild reaction conditions. The current method is also suitable for the synthesis of enantioenriched 4‐formyl‐β‐lactams and succinimides containing quaternary carbon centers.     

Co3O4/g-C3N4复合光催化剂降解罗丹明B的研究

为提高石墨相氮化碳(g-C3N4)的光催化性能,采用3D花状ZIF-Co与g-C3N4混合热处理的方法制备了3D花状Co3O4/g-C3N4复合光催化剂,并将其用于光催化降解罗丹明B模拟染料废水。结果表明:当ZIF-Co与g-C3N4的质量比为5%时,制备的Co3O4/g-C3N4的光催化性能最佳,在可见光下照射30 min,其对罗丹明B的降解率可达90%以上,且该催化剂的重复稳定性好。在降解罗丹明B的过程中活性基团的作用顺序为·O2->h+>·OH。     

Modeling the phase behavior of ternary systems ionic liquid + organic + CO2 with a Group Contribution Equation of State

This work presents the results of the use of a Group Contribution Equation of State (GC‐EOS) to model experimental data obtained for ternary systems of the type bmim[BF₄] + organic solute + CO₂ with four different organic compounds, namely acetophenone, 1‐phenylethanol, 4‐isobutylacetophenone, and 1‐(4‐isobutylphenyl)‐ethanol. Our results show that the GC‐EOS is able to qualitatively predict not only L+V→L but also L₁+L₂→L phase transitions. As the two two‐phase boundaries L+V and L₁+L₂ of the experimentally found three‐phase region L₁+L₂+V almost coincide with the saturated vapor pressure curve of pure CO₂, the phase transitions L+V→L₁+L₂+V and L₁+L₂+V→L₁+L₂ have been represented as this vapor‐pressure curve by the model. The average absolute deviations between experimental and predicted values for all phase transitions have been found to be very satisfactory. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

A Facile Method for the Synthesis of a MoS2/g‐C3N4 Photocatalyst

A MoS₂/g‐C₃N₄ composite was synthesized by a significantly simple method using Na₂MoO₄ and thiourea as precursors, without the need for a hydrothermal or an ultrasound step. The photocatalytic activity of the synthesized material was evaluated by the degradation of rhodamine B (RhB) in aqueous solution under blue light. The composites with low content of MoS₂ performed better than pure g‐C₃N₄. Using a low‐power light‐emitting diode light source, an improvement of two orders of magnitude in the photochemical space‐time yield was achieved, proving enhanced energy efficiency and productivity compared to earlier studies. The degradation pathway of organic pollutants was confirmed by the effects of selective scavengers.