Colorectal cancer-derived exosomes and modulation KRAS signaling.

Colorectal cancer (CRC) is one of the most common cancers worldwide and one of the main causes of cancer-associated mortality. At the period of diagnosis, metastases to other tissues will be present in around 30% of CRC individuals. Individuals with CRC continue to have a poor prognosis despite advances in medication. There is a growing body of literature that CRC develops as a result of the aggregation of various mutations in tumor oncogenes or suppressor genes and that diagnosing cancer in its initial phases may assist in increasing the overall lifespan of individuals with the illness. On the other hand, tumor cells may discharge exosomes in response to oncogenic mutations. By Inhibiting signaling pathways, including the Kirsten rat sarcoma virus (KRAS) mechanism, which is important in a variety of cell activities, exosomes have been shown to cause colorectal cancer in animal studies. The purpose of this review was to summarize the latest discoveries on the modulation of KRAS signaling by exosomes extracted from colorectal cancer.

Transformations of Aryl Ketones via Ligand-Promoted C-C Bond Activation.

The coupling of aromatic electrophiles (aryl halides, aryl ethers, aryl acids, aryl nitriles etc.) with nucleophiles is a core methodology for the synthesis of aryl compounds. Transformations of aryl ketones in an analogous manner via carbon-carbon bond activation could greatly expand the toolbox for the synthesis of aryl compounds due to the abundance of aryl ketones. An exploratory study of this approach is typically based on carbon-carbon cleavage triggered by ring-strain release and chelation assistance, and the products are also limited to a specific structural motif. Here we report a ligand-promoted ß-carbon elimination strategy to activate the carbon-carbon bonds, which results in a range of transformations of aryl ketones, leading to useful aryl borates, and also to biaryls, aryl nitriles, and aryl alkenes. The use of a pyridine-oxazoline ligand is crucial for this catalytic transformation. A gram-scale borylation reaction of an aryl ketone via a simple one-pot operation is reported. The potential utility of this strategy is also demonstrated by the late-stage diversification of drug molecules probenecid, adapalene, and desoxyestrone, the fragrance tonalid as well as the natural product apocynin.

The structures, water stabilities and photoluminescence properties of two types of iodocuprate(i)-based hybrids.

Although great progress has been made in hybrid iodocuprates(i) as lighting phosphors, the effects of aromatic and aliphatic structure directing agents (SDAs) on their water stability, structure and photoluminescence (PL) properties are still not clear. Herein, aromatic N-heterocyclic 1,2-di(4-pyridyl)ethylene (dpe), aliphatic N-heterocyclic 1,8-diazabicyclo[5.4.0]undec-7-ene (dbu) and N-aminoethylpiperazine (app) were selected to be SDAs to construct two types of hybrid iodocuprates(i) via a facile in situ approach. Aromatic dpe-derived cations are successfully directed to form (Me2dpe)(CuI3) (1), (Me2dpe)n(Cu4I6)n (2), (Et2dpe)2(Cu6I10) (3), and (H2dpe)n(Cu2I4)n (4). Three of them contain unprecedented inorganic iodocuprate clusters or chains. The aliphatic N-heterocyclic dbu- and app-derivative cations are responsible for the formation of (Hdbu)n(Cu2I3)n (5) and (H3app)2(Cu2I6)·2I·2H2O (6), which contain a (Cu2I3)- chain and a (Cu2I6)4- binuclear cluster, respectively. For the first time, the influence mechanisms of the water stabilities of iodocuprate-based PL materials were disclosed, by analyzing the possible interactions between SDAs and water molecules. 1-2 are PL silent due to their "self-quenching effect". 3, 4 and5 exhibit bright red, orange and yellow solid-state PL emissions at room temperature respectively, originating from the charge transfer between inorganic iodocuprate species and organic N-heterocycles. The co-template approach leads to multiple charge transfers in 6, which features a tunable PL behavior from bluish green to white by varying the excitation light, and has a quantum yield up to 43% (the highest value among hybrid iodocuprates containing (Cu2I6)4- clusters). The comparative study not only helps us to rationally synthesize iodocuprate-based PL materials with enhanced performance, but also provides a new method to obtain wavelength-dependent PL materials.

Ni-Al Bimetallic Catalyzed Enantioselective Cycloaddition of Cyclopropyl Carboxamide with Alkyne.

A Ni-Al bimetallic catalyzed enantioselective cycloaddition reaction of cyclopropyl carboxamides with alkynes has been developed. A series of cyclopentenyl carboxamides were obtained in up to 99% yield and 94% ee. The bifunctional-ligand-enabled bimetallic catalysis proved to be an efficient strategy for the C-C bond cleavage of unreactive cyclopropanes.

Nanocrystalline TiO2 Composite Films for the Photodegradation of Formaldehyde and Oxytetracycline under Visible Light Irradiation.

In order to effectively photodegradate organic pollutants, ZnO composite and Co-B codoped TiO2 films were successfully deposited on glass substrates via a modified sol-gel method and a controllable dip-coating technique. Combining with UV-Vis diffuse reflectance spectroscopy (DRS) and photoluminescence spectra (PL) analyses, the multi-modification could not only extend the optical response of TiO2 to visible light region but also decrease the recombination rate of electron-hole pairs. XRD results revealed that the multi-modified TiO2 film had an anatase-brookite biphase heterostructure. FE-SEM results indicated that the multi-modified TiO2 film without cracks was composed of smaller round-like nanoparticles compared to pure TiO2. BET surface area results showed that the specific surface area of pure TiO2 and the multi-modified TiO2 sample was 47.8 and 115.8 m²/g, respectively. By degradation of formaldehyde and oxytetracycline, experimental results showed that the multi-modified TiO2 film had excellent photodegradation performance under visible light irradiation.

Ligand-Accelerated Direct C-H Arylation of BINOL: A Rapid One-Step Synthesis of Racemic 3,3'-Diaryl BINOLs.

An ortho-selective rhodium-catalyzed direct C-H arylation of 1,1'-bi-2-naphthol (BINOL), to deliver the widely used but not easily available 3,3'-diaryl BINOL, has been developed. This highly efficient one-step synthetic approach is the shortest route to date and is greatly facilitated by the newly developed ligand system comprising tBu2 PCl, Ph2 -cod, and Cy3 P⋅HBF4 . In addition, the same procedure can facilitate the challenging syntheses of 3-bulkyaryl BINOLs in good to excellent yields.

A comparison study of aliphatic and aromatic structure directing agents influencing the crystal and electronic structures, and properties of iodoplumbate hybrids: water induced structure conversion and visible light photocatalytic properties.

The introduction of the aliphatic amines en (ethylenediamine), aep (N-(2-aminoethyl)piperazine) and tepa (tetraethylenepentamine), and the aromatic species 2,2'-bipy (2,2'-bipyridine) and dpe (1,2-di(4-pyridyl)ethylene) as structure directing agents (SDAs) into inorganic iodoplumbates affords six hybrids, namely [(Hen)4(H2.5O)2I](PbI6) (1), Cs2n[Pb3I8(en)2]n (2), (H3tepa)n(PbI5)n (3), (H2aep)n(PbI4)n (4), (Et22,2'-bipy)n(Pb2I6)n (5) and (Et2dpe)n(Pb2I6)n (6). 1 contains a discrete octahedral (PbI6)(4-) anion generated under the direction of a novel co-template, [(Hen)4(H2.5O)2I](4+). 2 contains inorganic Cs(+) ions and a novel hybrid anionic layer [Pb3I8(en)2]n(2n-) that has never been encountered in iodoplumbate hybrids. 3 features a zigzag (PbI5)(3-) chain with the charge being compensated by a triprotonated tepa cation. 4 is composed of perovskite sheets of lead(ii) octahedra and aep cations that are generated from tepa via an unprecedented in situ ligand reaction. Both 5 and 6 have (Pb2I6)n(2n-) chains and represent the first example of introducing a 2,2'-bipy or dpe derivative cation in iodoplumbate hybrids, respectively. The comparative study reveals that aliphatic amines and aromatic species contribute differently to the crystal and electronic structures, and the properties of the hybrids. Importantly, 1-4 exhibit interesting water induced structure conversions, while 5 and 6 can be used as heterogeneous photocatalysts for dye wastewater treatment under visible light irradiation.

Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo.

AIM: To assess BGC823 gastric cancer (GC) cell metastasis after knockdown of liver-intestine cadherin (CDH17) and the therapeutic value of CDH17-RNAi-lentivirus in vivo. METHODS: We evaluated primary tumor growth and assessed local infiltration and systemic tumor dissemination using an orthotopic implantation technique. The therapeutic value of CDH17 knockdown was examined by intratumoral administration of CDH17-RNA interference (RNAi)-lentivirus in an established GC tumor xenograft mouse model. Furthermore, a comparative proteomic approach was utilized to identify differentially expressed proteins in BGC823 and lenti-CDH17-miR-neg cells following CDH17 knockdown. RESULTS: Metastases in the liver and lung appeared earlier and more frequently in animals with tumors derived from BGC823 or lenti-CDH17-miR-neg cells than in tumors derived from lenti-CDH17-miR-B cells. Average tumor weight and volume in the CDH17-RNAi-lentivirus-treated group were significantly lower than those in the control group (tumor volume: 0.89 ± 0.04 cm³ vs 1.16 ± 0.06 cm³, P < 0.05; tumor weight: 1.15 ± 0.58 g vs 2.09 ± 0.08 g, P < 0.05). Fifteen differentially expressed proteins were identified after CDH17 silencing in BGC823 cells, including a variety of cytoskeletal and chaperone proteins as well as proteins involved in metabolism, immunity/defense, cell proliferation and differentiation, cell cycle, and signal transduction. CONCLUSION: Our data establish a foundation for future studies of the comprehensive protein expression patterns and effects of CDH17 in GC.

Overexpression of Dickkopf-3 induces apoptosis through mitochondrial pathway in human colon cancer.

AIM: To investigate the mechanisms of the biological roles of Dickkopf-3 (Dkk-3) in cell invasion, survival and apoptosis in colon cancer cells. METHODS: Three human colon cancer cell lines, i.e., HT-29, LoVo and SW480, were used. Overexpression of Dkk-3 induced by pEGFP-N1-Dkk-3-GFP plasmid in LoVo cells was performed using Lipofectamine 2000 reagent. Reverse transcription polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels of Dkk-3, respectively. Cell proliferation assay, cell cycle analysis, hoechst 33258 assay and Matrigel invasion assay were performed on Dkk-3 overexpressing transfectants. RESULTS: The mRNA and protein expressions of Dkk-3 in HT-29 (mRNA: 0.06 ± 0.02, protein: 0.06 ± 0.01) and LoVo (mRNA: 0.07 ± 0.02, protein: 0.07 ± 0.02) cells were significantly lower than that in SW480 cells (mRNA: 0.92 ± 0.04, protein: 0.69 ± 0.13; all P < 0.05), and the greatest levels of invasiveness was in LoVo cells. Dkk-3 overexpression inhibited the proliferation and invasion of LoVo cells and induced cell cycle arrest at G(0)/G(1) phase and subsequent apoptosis, as indicated by increased chromatin condensation and fragments, upregulated Bax and cytochrome c protein, downregulated survivin and Bcl-2 protein, and the activation of caspase-3 and caspase-9. Furthermore, Dkk-3 overexpression reduced the accumulation of cytosolic fraction of ß-catenin. CONCLUSION: Dkk-3 overexpression induced apoptosis in human colon cancer possibly through the mitochondrial pathway. Dkk-3 may be involved in the Wnt/ß-catenin signaling pathways in colon cancer.

P3HT as hole transport material and assistant light absorber in CdS quantum dots-sensitized solid-state solar cells.

Regioregular poly(3-hexylthiophene) (P3HT) was employed as a hole transport material and assistant light absorber for the fabrication of a CdS quantum dot-sensitized solid-state solar cell, by which a power-conversion efficiency of 1.42% was achieved under an AM1.5 G (100 mW cm(-2)) condition.

Blockade of proliferation and migration of gastric cancer via targeting CDH17 with an artificial microRNA.

Liver-intestine cadherin (CDH17) is a novel member of the cadherin superfamily implicated in gastric cancer progression. To determine the role of CDH17 in the process of gastric cancer invasive growth, in the present study, RNA interference mediated by recombinant lentivirus vectors expressing artificial CDH17 miRNA was applied to induce a long-lasting down-regulation of CDH17 gene expression in BGC823 cells. The expression levels of CDH17, tumor cell motility, migration potential, and pro-liferation were measured by flow cytometry, real-time RT-PCR, Western blot analysis, immunofluorescence staining, wound healing assay, and MTT assay, respectively. Results show that four recombinant plasmid expression vectors encoding pre-miRNA against CDH17, pcDNA-CDH17-miR-SR1, -SR2, -SR3, and -SR4 were constructed correctly and down-regulated the CDH17 mRNA levels by 5.5, 57, 91, and 98%, respectively, in BGC823 cells which had an overexpression of CDH17. We packaged the recombinant lentiviral vector for CDH17 RNA interference with pcDNA-CDH17-miR-SR4 which had the highest interfering efficiency and succeeded in construction of the stable transfectants. Of note, more than 90% knockdown of CDH17 expression in BGC823 cells was obtained by miRNA technique. The CDH17-miRNA-transfected cells showed significant decrease in cell proliferation, cell motility, and migration in comparison with the control cells. Thus, we proposed that CDH17 may be an oncogene up-regulating invasive features of gastric cancer cells and could be a hopeful target for the control of gastric cancer progression.

Lentiviral-mediated miRNA against liver-intestine cadherin suppresses tumor growth and invasiveness of human gastric cancer.

Liver-intestine cadherin (CDH17) represents a novel type of cadherin within the cadherin superfamily, and is distinguished from other cadherins by its distinct structural and functional features. Our previous studies had identified that increased CDH17 was significantly associated with tumor differentiation and lymph node metastasis in gastric cancer. In this study, we tested the hypothesis that CDH17 was associated with proliferation and invasiveness in gastric cancer using recombinant lentivirus-mediated miRNA targeting to CDH17 both in vitro and in vivo. We also detected the activity of matrix metalloproteinase (MMP)-2 and MMP-9 with gelatin zymography to explore the mechanisms underlying the inhibition of the CDH17 gene. Our results showed that a well-differentiated gastric cancer cell line had higher CDH17 expression. Down-regulation of CDH17 inhibited proliferation, adherence, and invasion of the poorly differentiated BGC823 gastric cancer cells in vitro, and induced cell cycle arrest. The activities of MMP-2 and MMP-9 were lower in the CDH17-miRNA-transfected cells compared to the control cells. Using an in vivo tumor growth assay, we confirmed that CDH17 silencing could obviously slow the growth of gastric cancer derived from BGC823 cells. Taken together, we have demonstrated that CDH17 maybe a positive regulator for proliferative, adhesive, and invasive behaviors of gastric cancer.

Perchloratobis[1-(1,10-phenanthrolin-2-yl)-2-pyridone]zinc(II) perchlorate.

In the title mononuclear complex, [Zn(ClO(4))(C(17)H(11)N(3)O)(2)]ClO(4), the Zn(II) ion is coordinated in a distorted octa-hedral geometry. The dihedral angles between the pyridine rings and the mean planes of the 1,10-phenanthroline ring system in each of the 1-(1,10-phenanthrolin-2-yl)-2-pyridone (PP) ligands is 24.51 (10)° for the tridendate PP ligand and 73.55 (6)° for the bidentate PP ligand. Within the mol-ecule there is a weak π-π inter-action between the pyridine ring of the bidentate ligand and the 1,10-phenanthroline ring system of the tridendate ligand with a centroid-centroid distance of 3.6383 (19) Å.

Diaqua-(1,10-phenanthrolin-2-ol)nickel(II) dinitrate.

In the mononuclear title complex, [Ni(C(12)H(8)N(2)O)(2)(H(2)O)(2)](NO(3))(2), the Ni(II) ion is coordinated in a distorted octa-hedral geometry. The dihedral angle between the two mean planes defined by the phenanthroline ligands is 88.26 (6)°. Intra- and intermolecular O-H⋯O hydrogen bonds between the cation and the anions lead to the formation of a layered arrangement parallel to (010).

Bis[mu-1-(1,10-phenanthrolin-2-yl)-2-pyridone]bis{aqua[1-(1,10-phenanthrolin-2-yl)-2-pyridone]cadmium(II)} tetrakis(perchlorate).

In the title centrosymmetric binuclear complex, [Cd2(C17H11N3O)4(H2O)2](ClO4)4, the Cd(II) ion assumes a distorted octahedral geometry. There are pi-pi stacking interactions between the pyridine and 1,10-phenanthroline ring systems of adjacent ligands at the same Cd(II) centre. Intermolecular hydrogen bonds between the coordinated aqua ligand and the O atom of a keto group connect adjacent complex cations into extended chains. Hydrogen bonds also exist between the complex cations and the perchlorate anions. Compared with the fluorescence spectrum of the organic ligand, the complex displays strong fluorescent emission and an ipsochromic shift of the emission peaks, which may be attributed to the structural character.

Aqua-(2-hydrazino-1,10-phenanthroline)nitratocopper(II) nitrate.

In the title mononuclear complex, [Cu(NO(3))(C(12)H(10)N(4))(H(2)O)]NO(3), the Cu(II) ion assumes a distorted square-pyramidal geometry. There is a π-π stacking inter-action between the five-membered ring containing the Cu atom and a pyridine ring of a neighboring complex [centroid-centroid distance = 3.567 (2) Šand a perpendicular distance of 3.394 Å]. The crystal structure also contains inter-molecular N-H⋯O, O-H⋯O and C-H⋯O hydrogen bonds, linking cations and anions. In addition, there is a short inter-molecular contact [2.784 (6) Å] between an O atom of the coordinated nitrate group and its symmetry-related atom.

Enhanced expression of cholecystokinin-2 receptor promotes the progression of colon cancer through activation of focal adhesion kinase.

Focal adhesion kinase (FAK) is suggested to be intimately involved in the progression of malignancies. Our previous research has demonstrated that activation of cholecystokinin-2 receptor (CCK2R) by gastrin stimulates a rapid activation of FAK pathway in human colon cancer cells. The purpose of this study is to determine the role of CCK2R and FAK in the progression of colon cancer. In this study, matched tissue samples of primary colon cancer and adjacent normal colon mucosa from the same patient were collected from 45 patients with colon cancer undergoing surgical resection. The gastrin expression was detected using reverse transcription polymerase chain reaction (RT-PCR). The CCK2R expression was examined by in situ hybridization and RT-PCR. The expression of FAK and phosphorylated FAK at tyrosine 397 (phospho-FAK) were detected using immunohistochemistry and immunoblotting. Colo320 and SW787, 2 colon cancer cell lines with or without CCK2R expression, were recruited in this study. Antisense oligonucleotide of FAK was used to block the expression of FAK. Invasiveness and motility of colon cancer cells were detected by Boyden chamber. In this series, enhanced expression of gastrin, CCK2R, FAK and phospho-FAK were observed in colon cancer tissues. CCK2R expression correlated with expression of phospho-FAK. Coexpression of CCK2R and phospho-FAK associated with invasion and lymph node metastasis. Increased invasion and motility was induced by gastrin in Colo320 cells. Overexpression of CCK2R by stable transfection of CCK2R plasmid amplified this increase and incubation with 1 microM L-365,260, a specific CCK2R antagonist, completely inhibited the effect of gastrin. FAK antisense largely blocked the increase of invasion and motility in Colo320 cells. Our data represent the evidence for the CCK2R regulating invasion and motility of colon cancer cells, and support a role of CCK2R in the progression of colon cancer. FAK play a critical role in this CCK2R-mediated effect.