Penehyclidine Hydrochloride Decreases Pulmonary Microvascular Endothelial Inflammatory Injury Through a Beta-Arrestin-1-Dependent Mechanism.

Penehyclidine hydrochloride (PHC), a type of hyoscyamus drug, has both antimuscarinic and antinicotinic activities and retains potent central and peripheral anticholinergic activities. Compared with other hyoscyamine, the notable advantage of PHC is that it has few M2 receptor-associated cardiovascular side effects. Recent studies and clinical trials have suggested that treatment with penehyclidine hydrochloride may also possess good effects in the treatment of lung injury. The mechanism responsible for this effect has yet to be determined; however, one possibility is that they might do so by a direct effect on pulmonary vascular endothelium. Since inflammatory reactions of the endothelium are signs of endothelial injury in the pathogenesis of lung injury, we determined the effects of penehyclidine hydrochloride on endothelial inflammatory injury in cultured human pulmonary microvascular endothelial cells (HPMVEC). Furthermore, human pulmonary microvascular endothelial cells were transfected with a shRNA-containing plasmid that specifically targets beta-arrestin-1 mRNA, to test whether the effect of penehyclidine hydrochloride on lipopolysaccharide (LPS)-induced endothelial cell injury is dependent on its upregulation of beta-arrestin-1 or not. Penehyclidine hydrochloride reduced the inflammatory responses to LPS stimulation, as evidenced by reduced lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), and interleukelin-6 (IL-6) levels, as well as vascular cell adhesion molecule 1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expressions. This was found to result from increased beta-arrestin-1 expression and decreased nuclear transcription factor-κB (NF-κB) activation. Expression of a shRNA-containing plasmid that specifically targets beta-arrestin-1 mRNA nullified these effects of penehyclidine hydrochloride. The results indicate that penehyclidine hydrochloride exerts a protective effect on pulmonary microvascular endothelial inflammatory injury induced by LPS. We also demonstrate that this is due to its ability to increase beta-arrestin-1, which in turn inhibits NF-κB activation.

Seamless stitching of graphene domains on polished copper (111) foil.

Seamless stitching of graphene domains on polished copper (111) is proved clearly not only at atomic scale by scanning tunnelling microscopy (STM) and transmission electron micoscopy (TEM), but also at the macroscale by optical microscopy after UV-treatment. Using this concept of seamless stitching, synthesis of 6 cm × 3 cm monocrystalline graphene without grain boundaries on polished copper (111) foil is possible, which is only limited by the chamber size.

Exploiting differential electrochemical stripping behaviors of Fe3O4 nanocrystals toward heavy metal ions by crystal cutting.

This study attempts to understand the intrinsic impact of different morphologies of nanocrystals on their electrochemical stripping behaviors toward heavy metal ions. Two differently shaped Fe3O4 nanocrystals, i.e., (100)-bound cubic and (111)-bound octahedral, have been synthesized for the experiments. Electrochemical results indicate that Fe3O4 nanocrystals with different shapes show different stripping behaviors toward heavy metal ions. Octahedral Fe3O4 nanocrystals show better electrochemical sensing performances toward the investigated heavy metal ions such as Zn(II), Cd(II), Pb(II), Cu(II), and Hg(II), in comparison with cubic ones. Specifically, Pb(II) is found to have the best stripping performance on both the (100) and (111) facets. To clarify these phenomena, adsorption abilities of as-prepared Fe3O4 nanocrystals have been investigated toward heavy metal ions. Most importantly, combined with theoretical calculations, their different electrochemical stripping behaviors in view of facet effects have been further studied and enclosed at the level of molecular/atom. Finally, as a trial to find a disposable platform completely free from noble metals, the potential application of the Fe3O4 nanocrystals for electrochemical detection of As(III) in drinking water is demonstrated.

Cytotoxic and anti-inflammatory prenylated benzoylphloroglucinols and xanthones from the twigs of Garcinia esculenta.

Five new prenylated benzoylphloroglucinol derivatives, garciesculentones A-E (1-5), a new xanthone, garciesculenxanthone A (6), and 15 known compounds were isolated from the petroleum ether extract and the EtOAc-soluble fraction of a 80% (v/v) EtOH extract of Garcinia esculenta. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analysis and mass spectrometry. Experimental and calculated ECD and a convenient modified Mosher's method were used to determine the absolute configurations. The cytotoxicity of these compounds were evaluated by MTT assay against three human cancer cell lines (HepG2, MCF-7, and MDA-MB-231) and against normal hepatic cells (HL-7702). In addition, these isolates were evaluated for their inhibitory effects on interferon-γ plus lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

Prenylated benzoylphloroglucinols and xanthones from the leaves of Garcinia oblongifolia with antienteroviral activity.

An acetone extract of the leaves of Garcinia oblongifolia showed antiviral activity against enterovirus 71 (EV71) using a cytopathic effect inhibition assay. Bioassay-guided fractionation yielded 12 new prenylated benzoylphloroglucinols, oblongifolins J-U (1-12), and five known compounds. The structures of 1-12 were elucidated by spectroscopic analysis including 1D- and 2D-NMR and mass spectrometry methods. The absolute configurations were determined by a combination of a Mosher ester procedure carried out in NMR tubes and ECD calculations. Compared to ribavirin (IC50 253.1 µM), compounds 1, 4, and 13 exhibited significant anti-EV71 activity in vitro, with IC50 values of 31.1, 16.1, and 12.2 µM, respectively. In addition, the selectivity indices of these compounds were 1.5, 2.4, and 3.0 in African green monkey kidney (Vero) cells, respectively.

[Survey on host animal and molecular epidemiology of hantavirus in Chuxiong prefecture, Yunnan province].

OBJECTIVE: To determine the hosts of hantavirus (HV) and its molecular epidemiological characteristics, to provide evidence for prevention and control on hemorrhagic fever with renal syndrome (HFRS). METHODS: Rodents were captured by a special trap within the residential area. The antigens of HV in lung tissues were detected by direct immuno-fluorescence assay (DFA). Nucleotide sequences of HV were amplified by RT-PCR with HV genotype-specific primer. The amplified genes were then sequenced. Phylogenetic tree were built on nucleotide sequence with ClustalX 1.83 software. RESULTS: 1421 rodents were captured and classified into 8 species of 4 Genera in the epidemic area within 10 counties of Chuxiong prefecture, Yunnan province, between 2005 and 2006. Out of the 1421 rodents, 1056 (74.31% ) of them were Rattus norvegicus and 280 (19.70%) belonged to Rattus flavipectus. The antigens of HV were detected by DFA in lung tissues and the total positive rate of HV was 5.15% (53/ 1029). After applying the sequencing nucleotide method to the 53 positive specimens, data showed that 21 specimens were positive and all of them belonged to Seoul type (15 samples were from Rattus norvegicus, 4 samples Rattus flavipectus, 2 samples Rattus nitidus). The partial S segments from 12 specimens were sequenced which appeared homologic with R22, L99 and HLD65 from GenBank in relatively high level (87.1% -99.7%). When compared to 76-118 strain of Hantaan type, their homologic degree was only 64.4%-69.1%. Results from Phylogenetic analysis showed that 12 specimens belonged to Seoul type. As for their homology, they were significantly similar to Seoul type and could be tentatively divided into two subtypes S1 and S3. CONCLUSION: It was confirmed that the Seoul type virus, as HFRS's pathogenetic agent mainly carried by rats, prevailed widely in Chuxiong prefecture. Owing to the local ecological environment, we also noticed the characteristics of different HV subtypes among Seoul type.