Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

[Research progress in drugs targeting 5-lipoxygenase for age-related diseases].

With the acceleration of aging society, delaying aging or promoting healthy aging has become a major demand for human health. 5-Lipoxygenase (5-LOX) is a key enzyme catalyzing arachidonic acid into leukotrienes (LTs), which is a potent mediator of the inflammatory response. Previous studies showed that abnormal activation of 5-LOX and overproduction of LTs are closely related to the occurrence and development of aging-related inflammatory diseases. Therefore, inhibiting 5-LOX activation is a possibly potential strategy for treating age-related diseases. In this paper, the latest research progress in 5-LOX activation, 5-LOX in mediating aging-related diseases and its small molecule inhibitors is briefly reviewed to provide scientific theoretical basis and new ideas for the prevention and treatment of aging-related inflammatory diseases.

Synthesis, cytotoxicity and inhibition of NO production of ivangustin enantiomer analogues.

The eight novel ivangustin enantiomer analogues possessing α-methylene-γ-butyrolactone moiety have been synthesized using (4S6R, 4S6S)-4-tert-butyldimethylsilyloxy-6-methylcyclohex-2-en-1-one (1) as starting material. These transformations were mainly carried out by aldol condensation reaction and one-pot annelation procedure. The stereochemistry of these synthesized analogues was determined by NOE analysis. Their cytoxicity was evaluated against the human cancer cell lines HCT-116 (colon), HL-60 (leukemia), QGY-7701 (liver), SMMC-7721 (liver), A549 (lung), MCF-7 (breast). The results showed that these analogues were more selective against the cell lines HL-60 and QGY-7701. Analogue 17 exhibited potent cytotoxicity and high selectivity toward HL-60 cell line with IC50 value of 1.02 µM, which suggested that it might be a promising anti-cancer lead compound. The inhibitory activities against NO production and the cytotoxicities in RAW 264.7 macrophages were determined at the same time. All of the analogues significantly inhibited the NO production with IC50 value in the range of 3.44-6.99 µM. Analogues 17, 22, 23 and 7 showed higher cytotoxicities, indicated their inhibitory activities against NO production may be influenced by the cytotoxicities.

New strategy to construct single-ion magnets: a unique Dy@Zn6 cluster exhibiting slow magnetic relaxation.

Two unique heptanuclear clusters Ln@Zn6 (Ln = Dy (1), Er (2)) were structurally and magnetically characterized. Each Dy(3+)/Er(3+) is located in a nona-coordinate D(3h) coordination environment, and is encapsulated in a diamagnetic Zn6 cage. Compound 1 exhibits single-ion magnetic behavior, and is the first example of a single-ion magnet (SIM) constructed through embedding one magnetic anisotropic metal ion into a diamagnetic cage.

Cloud-point extraction combined with liquid chromatography for the determination of ergosterol, a natural product with diuretic activity, in rat plasma, urine, and faeces.

Ergosterol from many medicinal fungi has been demonstrated to possess a variety of pharmacological activities in vivo and in vitro. A new method based on cloud-point extraction has been developed, optimized and validated for the determination of ergosterol in rat plasma, urine and faeces by liquid chromatography. The non-ionic surfactant Triton X-114 was chosen as the extract solvent. The chromatographic separation was performed on an Inertsil ODS-3 analytical column with a mobile phase consisting of methanol and water (98 : 2, v/v) at a flow rate of 1 mL/min. The methodology was validated completely. The results indicated good performance in terms of specificity, linearity, detection and quantification limits, precision and accuracy. The method was successfully applied to the pharmacokinetic studies of ergosterol in rats. The results indicate that the ergosterol levels in feces are much higher than those in plasma and urine of the rat.

Synthesis and application of a novel single-isomer mono-6-deoxy-6-((2S,3S)-(+)-2,3-O-isopropylidene-1,4-tetramethylenediamine)-ß-cyclodextrin as chiral selector in capillary electrophoresis.

A novel single isomer of positively charged ß-cyclodextrin, mono-6-deoxy-6-((2S,3S)-(+)-2,3-O-isopropylidene-1,4-tetramethylenediamine)-ß-CD (MIPTACD) was designed and synthesized in seven steps starting from commercially available (2R,3R)-tartaric acid. The chiral resolution abilities of the new cationic chiral selector were studied by capillary electrophoresis using 10 different dansyl (Dns)-amino acids and N-acetylphenylalanine (N-Ac-Phe) as model analytes. The effects of running buffer pH and chiral selector concentration on the separation selectivity, resolutions, and migration times of analytes were studied in detail. MIPTACD shows a very good chiral recognition ability even at very low concentrations at the investigated pH values, as shown by the very large values of selectivity and resolution towards amino acids enantiomers to be assessed.

Quantitative HPLC method and pharmacokinetic studies of ergosta-4,6,8(14),22-tetraen-3-one, a natural product with diuretic activity from Polyporus umbellatus.

A simple and specific HPLC method with dual wavelength UV detection for the determination of ergosta-4,6,8(14),22-tetraen-3-one (ergone) in rat plasma was developed and proved to be efficient. The method used ergosterol as internal standard (IS). Following a single-step protein precipitation, the analyte and IS were separated on an Inertsil ODS-3 column with a mobile phase containing methanol-water (99:1, v/v) at a flow rate of 1 mL/min. The analytes were detected by using UV detection at wavelength of 350 (ergone) and 283 (IS) nm, respectively. The calibration curve was linear over the range of 0.1-2.0 µg/mL and the lower limit of quantification was 0.1 µg/mL. The intra-day and inter-day precision studies showed good reproducibility with RSD less than 8.5%. The intra-day and inter-day accuracy ranged from 95.6 to 104%. Mean extraction recovery was above 95% at the low, medium and high concentrations. The present HPLC-UV method was simple and reliable. The method described herein had been successfully applied for the pharmacokinetic studies in male SD rats after administration of 20 mg/kg dose of solution of ergone.

Rapid resolution liquid chromatography-mass spectrometry and high-performance liquid chromatography-fluorescence detection for metabolism and pharmacokinetic studies of ergosta-4,6,8(14),22-tetraen-3-one.

Ergosta-4,6,8(14),22-tetraen-3-one (ergone) from many medicinal plants has been demonstrated to possess a variety of pharmacological activities in vivo and in vitro, including cytotoxic, diuretic and immunosuppressive activity. Metabolism and pharmacokinetic studies on rat were conducted for ergone. Rapid resolution liquid chromatography with atmospheric pressure chemical ionization tandem multi-stage mass spectrometry (RRLC-APCI-MS(n)) and high-performance liquid chromatography with fluorescence detection (HPLC-FLD) methods were applied for the identification and quantification of ergone and its metabolite from rat plasma, faeces and urine. A metabolite was identified by RRLC-DAD-APCI-MS(n): 22,23-epoxy-ergosta-4,6,8(14)-triaen-3-one (epoxyergone). The concentrations of the analyte with its metabolites were determined by HPLC-FLD at excitation wavelength of 370 nm and emission wavelength of 485 nm. The samples were deproteinized with methanol after addition of camptothecin as internal standard (IS). The analysis was performed on a Diamonsil C18 column (150 mm x 4.6 mm x 5 microm) with a mobile phase gradient consisting of methanol and water at a flow rate of 1 mL min(-1). The assay was linear over the concentration range of 42-1500, 36-7500 and 42-1500 ng mL(-1) for plasma, faecal homogenate and urine respectively. The absolute recoveries were found to be 97.0+/-1.2%, 98.1+/-0.7% and 96.6+/-1.8% for plasma, faecal homogenate and urine respectively. The intra-day and inter-day relative standard deviations (RSD) were less than 10%. The previous HPLC-MS/MS method is not affordable for most laboratories because of the specialty requirement and high equipment cost. However, the HPLC-FLD method is economic and operating simply for quantitative determination of ergone and its metabolite in rat plasma, faeces and urine. In addition, liquid chromatography coupled with ion trap multi-stage mass spectrometry is becoming a useful technique for ergone metabolite identification.

4,4,5,5-Tetra-methyl-2-[4-(2-pyrid-yl)phen-yl]-3,4-dihydro-imidazole-1-oxyl-3-oxide.

In the title compound, C(18)H(20)N(3)O(2), the pyridine and phenyl rings are coplanar [dihedral angle = 3.5 (3)°]. The phenyl ring makes a dihedral angle of 29.6 (1)° with the imidazole ring. The crystal structure is stabilized by inter-molecular C-H⋯O hydrogen bonds.

Determination of venlafaxine in human plasma by high-performance liquid chromatography using cloud-point extraction and spectrofluorimetric detection.

A new straightforward method based on cloud-point extraction (CPE) has been developed, optimized and validated for the determination of venlafaxine in human plasma by reversed-phase high-performance liquid chromatography with fluorescence detection. The non-ionic surfactant Triton X-114 (polyethylene glycol tert-octylphenyl ether) was chosen as the extract solvent. Separation was obtained using a reversed-phase Diamonsil column (C(18), 250 mm x 4.6 mm I.D., 5 microm) and a mobile phase composed of acetonitrile-phosphate buffer solution (pH 3.0)-triethylamine (33.5:66.5:0.4). Fluorescence detection was used (lambda(ex) 276 nm, lambda(em) 598 nm). Maprotiline was used as the internal standard. Under the optimum conditions, the linear range of venlafaxine in human plasma was 10-800 ng mL(-1) (r(2)=0.9995). The limit of detection (LOD) was less than 2 ng mL(-1) (S/N=3) and the limit of quantification (LOQ) was less than 10 ng mL(-1) (S/N=10). The method was successfully applied for the evaluation of pharmacokinetic profiles of venlafaxine capsules in nine healthy volunteers.

[Reconstruction of orbital margin defect with porous high-density polyethylene implanted material].

OBJECTIVE: To study the effects and safety of Medpor porous high-density polyethylene implanted material in the reconstruction of orbital margin defects. METHODS: Sixteen cases of orbital margin defects were treated with Medpor. RESULTS: The orbital margin defects in 16 cases with orbital defects were successfully treated with Medpor. During a follow-up of 1 to 4 years (averaged 2.4 years), there was no extrusion, absorption or migration of the implants. CONCLUSION: Medpor is a good substitute material of bone graft and is much better than other autologous tissues or other artificial materials.