DNA functionalization of colloidal particles via physisorption of azide-functionalized diblock copolymers.

DNA-coated inorganic particles can be prepared simply by physical adsorption of azide-functionalized diblock copolymers (polystyrene-b-poly(ethylene oxide)-azide, PS-b-PEO-N3) onto hydrophobically-modified inorganic particles, followed by strain-promoted azide-alkyne cycloaddition (SPAAC, copper-free click chemistry). This approach is applied to organosilica, silica and titania particles. The DNA-coated colloids are successfully crystallized into colloidal superstructures by a thermal annealing process using DNA-mediated assembly.

Si nanoparticle clusters in hollow carbon capsules (SNC@C) as lithium battery anodes: toward high initial coulombic efficiency.

Large volumetric expansion and structural pulverization have been major problems in Si-based anode materials for Li-ion batteries. To overcome this limitation, yolk-shell structured Si-carbon structures have been proposed to allow for the reversible structural breathing of Si nanoparticles confined inside the carbon shell. However, initial coulombic efficiency (ICE) of the yolk-shell structured anodes is highly decreased mainly due to their extremely high specific surface area (SSA) and the resulting excessive formation of solid electrolyte interphase (SEI) over the carbon shell. Here, instead of using a single Si nanoparticle-containing yolk-shell structure, we propose a novel structure comprising hollow carbon capsules internally encapsulating Si nanoparticle clusters (SNC@Cs). To implement this structural design, Si nanoparticle clusters are encompassed by a polystyrene matrix (SNC@PS) by emulsion polymerization, followed by coating with a polydopamine (PDA) layer (SNC@PS@PDA). Then, after annealing them for carbonization, SNC@Cs are finally prepared, which can decrease the SSA by a factor of one-third compared to the conventional yolk-shell structures. These SNC@C particles have shown remarkably high ICE values of up to 81%. Moreover, the cycling stability could be improved up to 100 cycles because the properly confined Si cluster inside the stable carbon capsule mitigates structural pulverization during repeated lithiation-delithiation processes of Si nanoparticles.

DNA-Functionalized 100 nm Polymer Nanoparticles from Block Copolymer Micelles.

DNA-mediated self-assembly of colloidal particles is one of the most promising approaches for constructing colloidal superstructures. For nanophotonic materials and devices, DNA-functionalized colloids with diameters of around 100 nm are essential building blocks. Here, we demonstrate a strategy for synthesizing DNA-functionalized polymer nanoparticles (DNA-polyNPs) in the size range of 55-150 nm using block copolymer micelles as a template. Diblock copolymers of polystyrene- b-poly(ethylene oxide) with an azide end group (PS- b-PEO-N3) are first formed into spherical micelles. Then, the micelle cores are swollen with the styrene monomer and polymerized, thus producing PS NPs with PEO brushes and azide functional end groups. DNA strands are conjugated onto the ends of the PEO brushes through a strain-promoted alkyne-azide cycloaddition reaction, resulting in a DNA density of more than one DNA strand per 12.6 nm2 for 70 nm particles. The DNA-polyNPs with complementary sequences enable the formation of CsCl-type colloidal superstructure by DNA binding.

Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer.

The most common therapy for estrogen receptor-positive breast cancer is antihormone therapy, such as tamoxifen. However, acquisition of resistance to tamoxifen in one third of patients presents a serious clinical problem. Polo-like kinase 1 (Plk1) is a key oncogenic regulator of completion of G2-M phase of the cell cycle. We assessed Plk1 expression in five chemoresistant cancer cell types and found that Plk1 and its downstream phosphatase Cdc25c were selectively overexpressed in tamoxifen-resistant MCF-7 (TAMR-MCF-7) breast cancer cells. Real-time monitoring of cell proliferation also showed that TAMR-MCF-7 cells were more sensitive to inhibition of cell proliferation by the ATP-competitive Plk1 inhibitor BI2536 than were the parent MCF-7 cells. Moreover, BI2536 suppressed expression of epithelial-mesenchymal transition marker proteins and 3D spheroid formation in TAMR-MCF-7 cells. Using TAMR-MCF-7 cell-implanted xenograft and spleen-liver metastasis models, we showed that BI2536 inhibited tumor growth and metastasis in vivo Our results suggest that Plk1 could be a novel target for the treatment of tamoxifen-resistant breast cancer. Mol Cancer Ther; 17(4); 825-37. ©2018 AACR.

Induction of methionine adenosyltransferase 2A in tamoxifen-resistant breast cancer cells.

We previously showed that S-adenosylmethionine-mediated hypermethylation of the PTEN promoter was important for the growth of tamoxifen-resistant MCF-7 (TAMR-MCF-7) cancer cells. Here, we found that the basal expression level of methionine adenosyltransferase 2A (MAT2A), a critical enzyme for the biosynthesis of S-adenosylmethionine, was up-regulated in TAMR-MCF-7 cells compared with control MCF-7 cells. Moreover, the basal expression level of MAT2A in T47D cells, a TAM-resistant estrogen receptor-positive cell line was higher compared to MCF-7 cells. Immunohistochemistry confirmed that MAT2A expression in TAM-resistant human breast cancer tissues was higher than that in TAM-responsive cases. The promoter region of human MAT2A contains binding sites for nuclear factor-κB, activator protein-1 (AP-1), and NF-E2-related factor 2 (Nrf2), and the activities of these three transcription factors were enhanced in TAMR-MCF-7 cells. Both the protein expression and transcriptional activity of MAT2A in TAMR-MCF-7 cells were potently suppressed by NF-κB inhibition but not by c-Jun/AP-1 or Nrf2 knock-down. Interestingly, the expression levels of microRNA (miR)-146a and -146b were diminished in TAMR-MCF-7 cells, and miR-146b transduction decreased NF-κB-mediated MAT2A expression. miR-146b restored PTEN expression via the suppression of PTEN promoter methylation in TAMR-MCF-7 cells. Additionally, miR-146b overexpression inhibited cell proliferation and reversed chemoresistance to 4-hydroxytamoxifen in TAMR-MCF-7 cells.

Carotenoid production from n-alkanes with a broad range of chain lengths by the novel species Gordonia ajoucoccus A2(T).

A novel diesel-degrading bacterial strain, A2(T), was isolated from soil that was heavily contaminated with oil. Based on phenotypic, phylogenetic, and DNA analyses, strain A2(T) was identified as a novel species of the genus Gordonia and named Gordonia ajoucoccus A2(T) (KCTC 11900BP and CECT8382). G. ajoucoccus A2(T) is able to synthesize carotenoids and produces mainly γ-carotene and keto-γ-carotene. G. ajoucoccus A2(T) is also capable of assimilating n-alkanes with a broad range of chain lengths (C6, C8-C25). Batch culture of G. ajoucoccus A2(T) in a bioreactor containing 1 % (v/v) hexadecane or 1 % (v/v) commercial diesel yielded 25 mg L⁻¹ and 2.6 mg L⁻¹ of carotenoids, respectively. Gas chromatography/mass spectrometry (GC-MS) analysis of hexadecane and hexane degradation metabolites suggested that G. ajoucoccus A2(T) may possess a terminal oxidation pathway that allows it to utilize n-alkanes and hexane as carbon and energy sources. G. ajoucoccus A2(T) could therefore serve as a good model system for understanding microbial n-alkane degradation pathways. Additionally, the metabolic capabilities of G. ajoucoccus A2(T) suggest potential biotechnological applications, such as the bioproduction of carotenoids from industrial discharge or other sources of n-alkanes.

Homicide and bipolar I disorder: a 22-year study.

BACKGROUND: Non-serious offenses in manic phase have been mainly studied in patients with bipolar disorder. However, some authors reported that depressive phase is related with the violent and homicidal manifestations of bipolar disorder. AIMS: We investigated the characteristics of homicide by the polarity of mood episode in patients with bipolar I disorder. METHODS: Among the offenders who were sentenced to undergo treatment at the National Institute of Forensic Psychiatry from October 1987 to January 2008, a total 219 offenders whose final diagnoses were bipolar I disorder based on DSM-III-R and DSM-IV were selected. Retrospective medical chart review was performed for characteristics of mood episodes. Descriptions of offenders were supplemented by review of the written records of the police or prosecutors. RESULTS: The general rate of total offense was higher in the manic phase than in the depressive phase (86.8% vs. 13.2%). However, the rate of homicide was higher in the depressive phase than in the manic phase. The victims of homicide were more likely to be family members of the patients in depressive phase than in manic phases (96.2% vs. 63.9%, p=0.001). However, parricide was committed only in manic phases. Altruistic motivation of homicide was significantly higher in depressive phase (34.6% vs. 0%, p<0.001) whereas impulsivity was the most common one in manic phases. CONCLUSIONS: The risk of offenses, particularly homicide for family members, should not be overlooked in the depressive phases of bipolar I disorder.

Bavachalcone inhibits osteoclast differentiation through suppression of NFATc1 induction by RANKL.

Osteoclasts are cells that have a specialized role for bone resorption and are responsible for many bone diseases such as osteoporosis. As herbal products are invaluable sources in discovery of compounds for new therapies, we sought to identify compounds efficacious in suppressing osteoclastogenesis from medicinal plants that have been implicated for treatment of osteoporotic conditions. Bavachalcone was isolated from Psoralea corylifolia, and its effects on osteoclast differentiation were evaluated with primary cultures of osteoclast precursor cells. In addition, the molecular mechanism of action was investigated. Bavachalcone inhibited osteoclast formation from precursor cells with the IC(50) of approximately 1.5 microg ml(-1). The activation of MEK, ERK, and Akt by receptor activator of nuclear factor kappaB ligand (RANKL), the osteoclast differentiation factor, was prominently reduced in the presence of bavachalcone. The induction of c-Fos and NFATc1, key transcription factors for osteoclastogenesis, by RANKL was also suppressed by bavachalcone. In conclusion, bavachalcone inhibits osteoclastogenesis by interfering with the ERK and Akt signaling pathways and the induction of c-Fos and NFATc1 during differentiation. Our results suggest that bavachalcone may be useful as a therapeutic drug for bone resorption-associated diseases.

Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 expression by xanthanolides isolated from Xanthium strumarium.

Three sesquiterpenoids, xanthatin (1), xanthinosin (2), and 4-oxo-bedfordia acid (3) were isolated from Xanthium strumarium as inhibitors of nitric oxide synthesis in activated microglia (IC(50) values: 0.47, 11.2, 136.5 microM, respectively). Compounds 1 and 2 suppressed the expression of iNOS and COX-2 and the activity of NF-kappaB through the inhibition of LPS-induced I-kappaB-alpha degradation in microglia.

Inhibition of nitric oxide synthase expression in activated microglia and peroxynitrite scavenging activity by Opuntia ficus indica var. saboten.

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO-), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. A butanol fraction obtained from 50% ethanol extracts of Opuntia ficus indica var. saboten (Cactaceae) stem (SK OFB901) and its hydrolysis product (SK OFB901H) inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50 15.9, 4.2 microg/mL, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at higher than 30 microg/mL as observed by western blot analysis and RT-PCR experiment. They also inhibited the degradation of I-kappaB-alpha in activated microglia. Moreover, they showed strong activity of peroxynitrite scavenging in a cell free bioassay system. These results imply that Opuntia ficus indica may have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.