Syntheses, Crystal Structures, and Magnetic Properties of Four New Cyano-Bridged Bimetallic Complexes Based on the <i>mer</i>-[Fe^III(qcq)(CN)₃]⁻ Building Block

Four new cyano-bridged bimetallic complexes, [{Mn^III(salen)}₂­{Fe^III(qcq)­(CN)₃}₂]_<i>n</i>·3<i>n</i>CH₃CN·<i>n</i>H₂O (<b>1</b>) [salen = <i>N</i>,<i>N</i>′-ethylenebis­(salicylideneiminato) dianion; qcq^– = 8-(2-quinoline-2-carboxamido)­quinoline anion], [{Mn^III(salpn)}₂­{Fe^III(qcq)­(CN)₃}₂]_<i>n</i>·4<i>n</i>H₂O (<b>2</b>) [salpn = <i>N</i>,<i>N</i>′-1,2-propylenebis­(salicylideneiminato)­dianion], [{Mn^II(bipy)­(CH₃OH)}­{Fe^III(qcq)­(CN)₃}₂]₂·2H₂O·2CH₃OH (<b>3</b>) (bipy = 2,2′-bipyridine), and [{Mn^II(phen)₂}­{Fe^III(qcq)­(CN)₃}₂]·CH₃CN·2H₂O (<b>4</b>) (phen = 1,10-phenanthroline) have been synthesized and characterized both structurally and magnetically. The structures of <b>1</b> and <b>2</b> are both unique 1-D linear branch chains with additional structural units of {Mn^III(salen/salpn)}­{Fe^III(qcq)­(CN)₃} dangling on the sides. In contrast, <b>3</b> and <b>4</b> are cyano-bridged bimetallic hexanuclear and trinuclear clusters, respectively. The intermolecular short contacts such as π–π interactions and hydrogen bonds extend <b>1</b>–<b>4</b> into high dimensional supermolecular networks. Magnetic investigation reveals the dominant intramolecular antiferromagnetic interactions in <b>1</b>, <b>3</b>, and <b>4</b>, while ferromagnetic and antiferromagnetic interactions coexist in <b>2</b>. Alternating current measurement at low temperature indicates the existence of slow magnetic relaxation in <b>1</b> and <b>2</b>, which should be due to the single ion anisotropy of Mn^III

Syntheses, Crystal Structures, and Magnetic Properties of Four New Cyano-Bridged Bimetallic Complexes Based on the <i>mer</i>-[Fe^III(qcq)(CN)₃]⁻ Building Block

Four new cyano-bridged bimetallic complexes, [{Mn^III(salen)}₂­{Fe^III(qcq)­(CN)₃}₂]_<i>n</i>·3<i>n</i>CH₃CN·<i>n</i>H₂O (<b>1</b>) [salen = <i>N</i>,<i>N</i>′-ethylenebis­(salicylideneiminato) dianion; qcq^– = 8-(2-quinoline-2-carboxamido)­quinoline anion], [{Mn^III(salpn)}₂­{Fe^III(qcq)­(CN)₃}₂]_<i>n</i>·4<i>n</i>H₂O (<b>2</b>) [salpn = <i>N</i>,<i>N</i>′-1,2-propylenebis­(salicylideneiminato)­dianion], [{Mn^II(bipy)­(CH₃OH)}­{Fe^III(qcq)­(CN)₃}₂]₂·2H₂O·2CH₃OH (<b>3</b>) (bipy = 2,2′-bipyridine), and [{Mn^II(phen)₂}­{Fe^III(qcq)­(CN)₃}₂]·CH₃CN·2H₂O (<b>4</b>) (phen = 1,10-phenanthroline) have been synthesized and characterized both structurally and magnetically. The structures of <b>1</b> and <b>2</b> are both unique 1-D linear branch chains with additional structural units of {Mn^III(salen/salpn)}­{Fe^III(qcq)­(CN)₃} dangling on the sides. In contrast, <b>3</b> and <b>4</b> are cyano-bridged bimetallic hexanuclear and trinuclear clusters, respectively. The intermolecular short contacts such as π–π interactions and hydrogen bonds extend <b>1</b>–<b>4</b> into high dimensional supermolecular networks. Magnetic investigation reveals the dominant intramolecular antiferromagnetic interactions in <b>1</b>, <b>3</b>, and <b>4</b>, while ferromagnetic and antiferromagnetic interactions coexist in <b>2</b>. Alternating current measurement at low temperature indicates the existence of slow magnetic relaxation in <b>1</b> and <b>2</b>, which should be due to the single ion anisotropy of Mn^III

Cytotoxic effect of ARG on HCC cells and normal hepatic cells.

<p>(A) Hep G2, SMMC7721 and LO2 cell lines were treated with ARG at 5, 10, 20, 50, 80, 100 μM for 24 h. (B) Hep G2 cells were exposed to a gradient dose of ARG for the indicated time period and IC₅₀ value was calculated for each time point. Cell viability inhibition was assessed by MTT assay. Each value is the mean ± SD of five independent experiments. *p<0.05, **p<0.01, ***p<0.0001 significant difference between control and ARG-treated cells in each cell line, as analyzed by Dunnett’s Multiple Comparion Test.</p

Mechanism of Arctigenin-Induced Specific Cytotoxicity against Human Hepatocellular Carcinoma Cell Lines: Hep G2 and SMMC7721

<div><p>Arctigenin (ARG) has been previously reported to exert high biological activities including anti-inflammatory, antiviral and anticancer. In this study, the anti-tumor mechanism of ARG towards human hepatocellular carcinoma (HCC) was firstly investigated. We demonstrated that ARG could induce apoptosis in Hep G2 and SMMC7721 cells but not in normal hepatic cells, and its apoptotic effect on Hep G2 was stronger than that on SMMC7721. Furthermore, the following study showed that ARG treatment led to a loss in the mitochondrial out membrane potential, up-regulation of Bax, down-regulation of Bcl-2, a release of cytochrome c, caspase-9 and caspase-3 activation and a cleavage of poly (ADP-ribose) polymerase in both Hep G2 and SMMC7721 cells, suggesting ARG-induced apoptosis was associated with the mitochondria mediated pathway. Moreover, the activation of caspase-8 and the increased expression levels of Fas/FasL and TNF-α revealed that the Fas/FasL-related pathway was also involved in this process. Additionally, ARG induced apoptosis was accompanied by a deactivation of PI3K/p-Akt pathway, an accumulation of p53 protein and an inhibition of NF-κB nuclear translocation especially in Hep G2 cells, which might be the reason that Hep G2 was more sensitive than SMMC7721 cells to ARG treatment.</p></div

ARG induced the changes of apoptotic proteins related to extrinsic pathways.

<p>Hep G2 and SMMC7721 cells were incubated with ARG (0, 1.56, 12.5, 100 μM) for 12 h and 24 h respectively, and then harvested for investigating the TNF-α, Fas and FasL expression level by western blot. The data represent mean ± SD of three separate experiments. Significant differences from control were indicated as *p<0.05, **p<0.01, ***p<0.0001.</p

ARG promotes HCC cells to undergo apoptosis.

<p>(A) Hep G2, SMMC7721 and LO2 cells treated with ARG (0, 1.56, 12.5, 100 μM) for 24 h were double-stained with Annexin V-FITC/PI and analyzed by flow cytometry. Quantification of population rate of early apoptotic cells (Annexin V+/PI− cells, lower right quadrant) and late apoptotic cells (Annexin V+/PI+ cells, upper right quadrants) were shown. Data represent the mean ± SD of triplicate experiments. Significant differences from vehicle-treated control were indicated as *p<0.05, **P<0.01, ***P<0.0001 in each cell line. (B) HepG2 and SMMC7721 cells were treated with ARG at the concentration of 20 μM for 48 h. The nuclei morphology changes were analyzed by Hoechst 33342 staining and the immunofluorescence analysis of cleaved caspase-3 are visualized using the cleaved caspase-3 antibody. The cellular fluorescent changes were observed by fluorescence microscope. At least 200 cells were counted to score the percentage of apoptotic cells which contained both cleaved caspase-3 and condensed and highly fluorescent nuclei fragments in each treatment group. Significant differences from control group were indicated as ***P<0.0001 in each cell line.</p

ARG caused the disfunction of mitochondrial membrane in HCC cells.

<p>Hep G2 and SMMC7721 cells were exposed to ARG (0, 1.56, 12.5, 100 μM) for 12 h and 24 h respectively. (A) Flow cytometric detection of Δ<i>Ψ</i>_<i>m</i> in HCC cells using JC-1. (B) The expression of Bcl-2 and Bax were analyzed by western blot with the loading control of β-actin. (C) Mitochondrial and cytoplasmic extracts were measured for Cyt c levels. Purity of the extracts was verified by β-actin (cytoplasmic) and COX IV (mitochondrial) expressions. Data were represented as mean ± SD of three separate experiments. Significant differences from control were indicated *p<0.05, **p<0.01, ***p<0.0001.</p

The apoptotic pathways induced by ARG in Hep G2 cell line.

<p>The apoptotic pathways induced by ARG in Hep G2 cell line.</p

Identification of Human Host Proteins Contributing to H5N1 Influenza Virus Propagation by Membrane Proteomics

The highly pathogenic avian influenza (HPAI) H5N1 virus is a highly virulent pathogen that causes respiratory diseases and death in humans and other animal species worldwide. Because influenza is an enveloped virus, the entry, assembly, and budding of virus particles are essential steps in the viral life cycle, and the virus relies on the participation of host cellular membrane proteins for all of these steps. Thus, we took a comparative membrane proteomics approach by using 2-DE coupled with MALDI-TOF/TOF MS to profile membrane proteins involved in H5N1 virus infection at 6, 12, and 24 h. Forty-two different proteins were found to vary on A549 cells due to H5N1 virus infection. Of these proteins, 57% were membrane or membrane-associated proteins. To further characterize the roles of novel identified proteins in virus propagation, the siRNA technology were applied and complement component C1q binding protein, annexin 2, prohibitin, peroxiredoxin 1 and heat shock protein 90-beta were successfully demonstrated to be contributed to viral propagation. In conclusion, the present study provides important new insight into understanding the roles of host membrane proteins in viral infection progress, and this insight is of particular importance for the development of novel therapeutic strategies

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<p>Tumor necrosis factor receptor-associated factor 3 (TRAF3), an intracellular signal transducer, is identified as an important component of Toll-like receptors and RIG-I-like receptors induced type I interferon (IFN) signaling pathways. Previous studies have clarified TRAF3 function in mammals, but little is known about the role of TRAF3 in ducks. Here, we cloned and characterized the full-length duck TRAF3 (duTRAF3) gene and an alternatively spliced isoform of duTRAF3 (duTRAF3-S) lacking the fragment encoding amino acids 217–319, from duck embryo fibroblasts (DEFs). We found that duTRAF3 and duTRAF3-S played different roles in regulating IFN-β production in DEFs. duTRAF3 through its TRAF domain interacted with duMAVS or duTRIF, leading to the production of IFN-β. However, duTRAF3-S, containing the TRAF domain, was unable to bind duMAVS or duTRIF due to the intramolecular binding between the N- and C-terminal of duTRAF3-S that blocked the function of its TRAF domain. Further analysis identified that duTRAF3-S competed with duTRAF3 itself for binding to duTRAF3, perturbing duTRAF3 self-association, which impaired the assembly of duTRAF3-duMAVS/duTRIF complex, ultimately resulted in a reduced production of IFN-β. These findings suggest that duTRAF3 is an important regulator of duck innate immune signaling and reveal a novel mechanism for the negative regulation of IFN-β production via changing the formation of the homo-oligomerization of wild molecules, implying a novel regulatory role of truncated proteins.</p