Direct growth of ordered PdCu and Co doped PdCu nanoparticles on graphene oxide based on a one-step hydrothermal method for ultrasensitive sensing of H2O2 in living cells.

Ordered PdCu and Co doped PdCu nanoparticles have been synthesized on graphene oxide (GO). The obtained Co-PdCu/GO composites were used to fabricate a H2O2 electrochemical sensor which exhibits an ultralow LOD (limit of detection) of 1.2 nM and an extra broad linear range of 5 nM-5.774 mM, and has been used to detect H2O2 in living cells successfully.

[Impacts of high-volume hemofiltration on hemodynamics and vascular endothelial permeability in children with septic shock].

OBJECTIVE: To investigate the effects of high-volume hemofiltration (HVHF) on hemodynamics, vasoactive factors, and vascular endothelial permeability in children with septic shock by a comparative analysis. METHODS: Thirty-six children who were diagnosed with septic shock between January 2013 and September 2014 were randomly divided into control and observation groups (n=18 each). Children in the control group were treated with the standard-volume hemofiltration (SVHF), while children in the observation group were treated with HVHF. The hemodynamic indices and levels of vasoactive factors including 6-keto-prostaglandin F1α (6-keto-PGF1α), thromboxane B2 (TXB2), soluble E-selectin (sE-selectin), and endothelium-derived relaxing factor (EDRF) were determined before and after treatment. In addition, the effects of ultrafiltrate on endothelial cell permeability were assessed. RESULTS: Compared with the control group, the observation group had significantly higher mean arterial pressure, significantly higher blood oxygen saturation, and a significantly lower heart rate after treatment (P<0.05). The levels of TXB2 and sE-selectin were significantly lower in the observation group than in the control group (P<0.05), while the levels of 6-keto-PGF1α and EDRF were significantly higher in the observation group than in the control group (P<0.05). Compared with the control group, the ultrafiltrate significantly attenuated the transepithelial electrical resistance in the observation group (P<0.05). CONCLUSIONS: Compared with SVHF, HVHF is a more effective approach for improving the hemodynamics and levels of vasoactive factors and reducing the vascular endothelial permeability in children with septic shock.

Reversible switches of DNA nanostructures between "Closed" and "Open" states and their biosensing applications.

A novel and versatile biosensing platform based on the structural conversion of 3D DNA nanostructures from ETDNA (Equilateral Triangle) to TPFDNA (Triangular Pyramid Frustum) was proposed for the first time. The inputs of aptamers and their relative targets made the DNA structure change from the "Open" to the "Closed" state, leading to the faradaic impedance changes as the output signals. The specific properties of excellent stability and specific rigid structure of 3D DNA nanostructures made the biosensor function as a regenerable, reusable and intelligent platform. The sensor exhibited excellent selectivity for IFN-γ detection with a wide linear range of 1.0 × 10(-9) to 2.0 × 10(-6) M and a low detection limit of 5.2 × 10(-10) M. The distinctive features of DNA nanostructures make them potentially advantageous for a broad range of biosensing, bionanoelectronics, and therapeutic applications.

Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-κB signaling pathway with distinct mechanisms.

AIM: Curcumin has shown promising anticancer activity, which relies on its inhibition on NF-κB pathway. In this study, we characterized the pharmacological profile of a novel curcumin analog P1 and elucidate the related mechanisms. METHODS: HEK293/NF-κB cells, stably transfected with an NF-κB-responsive luciferase reporter plasmid, were generated for high-throughput screen (HTS). Eight cancer cell lines, including PC3, COLO 205, HeLa cells etc. were tested. Cell viability was assessed using the sulforhodamine B (SRB) assays. Cell apoptosis was evaluated using FACS, immunocytochemistry, and Western blotting. H2-DCFDA and MitoSOX Red were used to detect cellular and mitochondrial reactive oxygen species (ROS). The mitochondrial function was evaluated using mitochondrial oxygen consumption assay. RESULTS: P1, a tropinone curcumin, was found in HTS targeting the NF-κB pathway. Its IC50 value in inhibition of TNF-α-induced NF-κB activation was 0.8 µmol/L, whereas its IC50 values in inhibiting the growth of A549 and HeLa cells were 1.24 and 0.69 µmol/L, respectively, which was 20- to 30-fold more potent than curcumin. The inhibition of P1 on the NF-κB pathway was further addressed in HeLa cells. The compound up to 10 µmol/L did not affect the binding of NF-κB to DNA, but markedly inhibited NF-κB nuclear translocation, IκB degradation and IκB kinase phosphorylation. The compound (1 and 3 µmol/L) concentration-dependently induced ROS generation, whereas curcumin up to 20 µmol/L had no effect. P1-induced ROS generation was mainly localized in mitochondria, and reversed by NAC. Moreover, the compound significantly enhanced TNF-α-induced apoptosis. CONCLUSION: P1 is a novel curcumin analog with potent anticancer activities, which exerts a distinct inhibition on the NF-κB pathway.

Revealing binding interaction between seven drugs and immobilized ß2-adrenoceptor by high-performance affinity chromatography using frontal analysis.

The development of new approaches to study the affinity between ligands and G-protein-coupled receptors proves to be of growing interest for pharmacologists, chemists, and biologists. The aim of this work was to determine the binding of seven drugs to ß2-adrenoceptors by frontal analysis using immobilized receptor stationary phase. The dissociation constants (Kd ) were determined to be (3.16 ± 0.09) × 10(-4) M for salbutamol, (4.29 ± 0.12) × 10(-4) M for terbutaline, (6.19 ± 0.16) × 10(-4) M for methoxyphenamine, (2.11 ± 0.07) × 10(-4) M for tulobuterol, (1.82 ± 0.11) × 10(-4) M for fenoterol, (9.75 ± 0.24) × 10(-6) M formoterol, and (9.84 ± 0.26) × 10(-5) M for clenbuterol. These results showed a good correlation with the data determined by radioligand binding assay. Further investigations revealed that the dissociation constant mainly attributed to the number of hydrogen bonds in the structures of ligands. This study indicates that affinity chromatography using immobilized receptor stationary phase can be used for the direct determination of drug-receptor binding interactions and has the potential to become a reliable alternative for quantitative studies of ligand-receptor interactions.

Discovery of di-indolinone as a novel scaffold for protein tyrosine phosphatase 1B inhibitors.

A series of di-indolinone derivatives was designed and synthesized to optimize our lead compounds basing on molecular docking study as PTP1B inhibitors. Successive enzymatic assay identified the synthetic di-indolinone as novel PTP1B inhibitors with low micromole-ranged inhibitory activity and at least several-fold selectivity over other tested homologous PTPs.

Synthesis and biological evaluation of noscapine analogues as microtubule-interfering agents.

A series of noscapine analogues have been synthesized via 13-step reaction starting from 2-hydroxy-3-methoxybenzaldehyde. Anti-tumor activities of these compounds were evaluated against HL-60 cell lines in vitro by the standard MTT assay. It was found that most of these derivatives showed appreciable inhibitory activity against HL-60 and tubulin polymerization. The results also indicated that the potency of compound 31 is about three times more than that ofnoscapine against HL-60 cell line and tubulin polymerization. Moreover, it induced a massive accumulation of cells in G2/M phase. These results showed noscapine and its derivatives were worth to be intensively studied further.

Distribution of phenolic acids in different tissues of jujube and their antioxidant activity.

Free, esterified, glycosided, and insoluble-bound forms of eight phenolic acids in pulp, seed, and peel of jujube are separated and quantified by high performance liquid chromatography with electrochemical detection (HPLC-ECD). In the whole jujube, p-hydroxybenzoic and cinnamic acids are the most abundant phenolic acids. All quantified phenolic acids are mainly present in jujube peel. Phenolic acids in seed and peel are present in the insoluble-bound form, while, in pulp in the glycosided form, the glycosided and insoluble-bound phenolic acid fractions in jujube pulp represent the highest total phenolic content and the strongest antioxidant activity determined by DPPH and FRAP assays. Our results show that most phenolic compounds with antioxidant activity in different tissues of jujube are present as the glycosided and insoluble-bound forms.

An ionic liquid supported CeO2 nanoparticles-carbon nanotubes composite-enhanced electrochemical DNA-based sensor for the detection of Pb2.

An electrochemical sensor incorporating a signal enhancement for the determination of lead (II) ions (Pb2+) was designed on the basis of the thrombin-binding aptamer (TBA) as a molecular recognition element and ionic liquid supported cerium oxide (CeO2) nanoparticles-carbon nanotubes composite modification. The composite comprises nanoparticles CeO2, multi-wall carbon nanotubes (MWNTs) and hydrophobic room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4). The electrochemical sensors were fabricated by immersing the CeO2-MWNTs-EMIMBF4 modified glassy carbon electrode (GCE) into the solution of TBA probe. In the presence of Pb2+, the TBA probe could form stable G-quartet structure by the specific binding interactions between Pb2+ and TBA. The TBA-bound Pb2+ can be electrochemically reduced, which provides a readout signal for quantitative detection of Pb2+. The reduction peak current is linearly related to the concentration of Pb2+ from 1.0×10-8 M to 1.0×10-5 M with a detection limit of 5×10-9 M. This work demonstrates that the CeO2-MWNTs-EMIMBF4 nanocomposite modified GCE provides a promising platform for immobilizing the TBA probe and enhancing the sensitivity of the DNA-based sensors.

[Synthesis of 1-furfuryl-indolin-2-one derivatives and preliminary evaluation of their antitumor activities].

In order to find new indolin-2-one derivatives as antitumor agents, a series of 3-pyrrole substituted 1-(5-formyl-2-furanylmethyl) indolin-2-one derivatives were designed and synthesized. 5-Formyl-2 ,4-dimethyl-lH-pyrrole-3-carboxylic acid ethyl ester was condensed with 5-substituted indolin-2-one 2a-2d to afford 3-[(pyrrol-2-yl) -methylidenyl] indolin-2-ones 3a-3d. Through N-alkylation, 1-(5-formyl-furfuryl) -indolin-2-one 4a-4d were prepared. Compounds 4a-4d were then condensed with indolin-2-one to afford bis-indolin-2-one derivatives 5a-5d. The structures of the synthesized compounds were determined by 1H NMR, MS and element analysis. Antitumor activities of all the synthesized compounds in vitro were tested. All the 12 synthesized compounds possess antitumor activities against SPC-A1 strain. Especially the compounds 5a-5d possess potent antitumor activities better than sunitinib. Their IC50 are all below 5 micromol x L(-1).

[HPLC-ESI-MS(n) analysis of the water soluble extracts of Fructus Choerospondiatis].

OBJECTIVE: To establish an HPLC-ESI-MS(n) method for analyzing the chemical ingredients in the water soluble extracts of Fructus Choerospondiatis. METHODS: Water-solvable extracts of Fructus Choerospondiatis are obtained by heating recirculation. Multi-stage reaction mode (MRM) of the HPLC-ESI-MS(n) was used to determine the content of Gallic acid, the MS(n) technology was used to obtain the information of characteristic multistage fragment ions so as to identify the chemical structure of peaks in the total current spectrum. RESULT: Eleven compounds were identified, and one of them is a new unknown ingredient. CONCLUSION: The method, which has high recovery and specificity, can offer the experimental evidences for the further research of the chemical ingredients extracted from the Fructus Choerospondiatis.

Hydrogen bonding and pi-pi stacking in dimethylgenistein.

The title compound, 5-hydroxy-4',7-dimethoxyisoflavone, C17H14O5, is composed of a benzopyranone moiety, a phenyl moiety and two methoxy groups. The benzopyranone ring is not coplanar with the phenyl ring, the dihedral angle between them being 56.28 (3) degrees. The two methoxy groups are nearly coplanar with their corresponding rings, having C-C-O-C torsion angles of 2.9 (2) and 5.9 (2) degrees . The molecules are linked by C-H...O hydrogen bonds into sheets containing classical centrosymmetric R2(2) (8) rings. The sheets are further linked by aromatic pi-pi stacking interactions and C-H...O hydrogen bonds into a supramolecular structure.

[Synthesis of 1-indole substituted beta-carboline alkaloid and its derivatives and evaluation of their preliminary antitumor activities].

AIM: To synthesize eudistomin U and its 6-OCH3/Br derivatives and 5'-Br derivatives as antitumor agents. METHODS: Using tryptamine and indole-3-aldehyde as starting materials, through condensation, Pictet-Spengler cyclization and dehydrogenation three steps, the alkaloids and its derivatives were prepared. RESULTS: The structures of the compounds were determined by 1HNMR, MS and HRMS. Antitumor activity in vitro was tested. CONCLUSION: Eudistomin U and its derivatives were synthesized. The results showed that they all showed antitumor activities against mouse P388 strain.

Anticarcinogenic and antioxidant activity of diindolylmethane derivatives.

AIM: To investigate the synthesis methods and the bioactivity of diindolylmethane (DIM) derivatives. METHODS: 1) A 3D-Quantitative Structure-Active Relationships (QSAR) Comparative Molecular Field Analysis (CoMFA) study of 14 DIM derivatives was investigated to predict their anticarcinogenic activity. 2) Based on CoMFA model, a series of new derivatives of DIM were designed and synthesized. 3) Their free radical scavenging and antioxidant potentials were tested using in-vitro DPPH radical scavenging and ?-carotene antioxidant models. 4) The anticarcinogenic activities of some compounds were tested by using microculture tetrazolium assay (MTT) and sulforhodamine B (SRB) proteochromosomic assays. RESULTS: 1) The CoMFA model derived from DIM analogues proved a good predictive ability with q2 value of 0.827. 2) New designed compounds 3c and 4c exhibited 3-fold more potent radical scavenging activity than reference substance Vitamin E in DPPH model expressed by IC50 values. 3) The primary antitumor screening essay showed that some DIM derivatives designed exhibited the inhibitory activities to some tumor cell growth at relatively high concentration, and DIM was the most effective among them. CONCLUSION: DIM's 3D-QSAR model is reliable. According to it, eleven DIM derivatives were synthesized, and two derivatives of them possess potent radical scavenging activities and some showed the inhibitory activities in primary anticancer assay in vitro.