Thionicotinamide-capped gold nanoparticles undergo fusion as well as fragmentation upon laser pulse excitation (532 nm). The aggregation effect which is induced by thionicotinamide also disappears following laser pulse excitation. The morphological changes induced by thermal and photochemical effects were found to influence the optical properties of these particles.Self-assembled monolayers (SAM) of organic compounds containing thio or amino functional groups provide a unique way to organize molecules and semiconductor nanoclusters on gold surfaces (see, for example, refs 1 and 2). Attempts have been made in recent years to modify gold nanoparticles with thio compounds. 3-8 Although recent efforts address the issues related to bulk SAM-gold surfaces, spectroscopic studies related to thio-capped gold nanoclusters 9-12 are rather limited. Interaction of thio compounds with gold nanoclusters in solution often leads to aggregation effects. Such an aggregation is noted by the appearance of a broad band in the red-infrared region. Recent laser-induced photochemical studies of metal nanoclusters have noted interesting photophysical properties such as transient plasmon bleaching, electron ejection, and photofragmentation. [13][14][15][16][17] We report here visible laser induced transformations of thionicotinamide gold nanoparticles and the spectral properties associated with changes in the morphology of these particles.Gold colloids were prepared by the conventional citric acid reduction of HAuCl 4 in water with sodium citrate at near-boiling temperature. 18 Surface modification of gold colloids was carried out by adding controlled amounts of thionicotinamide (TNA) to the ruby-colored colloidal gold suspension at room temperature. Transmission electron microscopic examination (TEM) was conducted by applying a drop of the colloid sample to a carbon-coated copper grid. Particle sizes were determined from the photographs taken at a magnification of 150 000 using a Hitachi H600 transmission electron microscope. The laser irradiation was carried out in a quartz cuvette (10 mm × 2 mm) with continuous N 2 bubbling. Laser irradiation experiments were performed using a mode-locked, Q-switched Continuum YG-501 DP Nd:YAG laser system (pulse width ∼ 18ps; λ ) 532 nm, output 1.5 mJ pulse). 17 The absorption spectra of gold nanoclusters in aqueous solutions before and after the complexation with thionicotinamide are shown in Figure 1 (spectra a and b, respectively). The native gold colloids exhibit a prominent surface plasmon band at 520 nm. At relatively high thionicotinamide concentrations the colloidal suspension turns blue and an absorption band in the red-infrared region (λ max ∼ 750 nm) appears. Such a broad band is indicative of aggregation and/or changes in the shape of gold nanoclusters. As indicated earlier, 19 the position of this Figure 1. (a) Absorption spectrum of 0.5 mM gold colloids in water.Absorption spectra of TNA-capped gold colloids (0.5 mM gold colloidal suspension containing 3 mM thionicotinamide) were recorded...

A mechanistic investigation on the photocatalytic reduction of CO2 with hexagonal CdS nanocrystallites prepared in N,N-dimethylformamide (DMF) was carried out from the standpoint of surface structures of the nanocrystallites. A remarkable increase of photocatalytic activity could be achieved by addition of excess Cd2+ to the system. Analysis of the emission behavior depending on the amount of excess Cd2+ in the system suggests that the Cd2+ addition results in the formation of sulfur vacancies on the surface of nanocrystallites due to the adsorption of excess Cd2+ to the surface. The formation of the sulfur vacancies on the surface was supported by in situ Cd K-edge EXAFS analysis of the nanocrystallites in solution as changes in the coordination numbers of cadmium−sulfur and cadmium−oxygen. Theoretical MO calculations using a density functional (DF) method supported the preferential bidentate-type absorption of CO2 with the Cd atom in the vicinity of the sulfur vacancy.

The major clearance mechanism of pravastatin, valsartan, and temocapril appears to be similar, and OATP1B1*1b is one of the determinant factors governing the interindividual variability in the pharmacokinetics of pravastatin and, possibly, valsartan and temocapril.

Hexagonal ZnS nanocrystallites (ZnS−DMF(OAc); ca. 2 nm in diameter) prepared in N,N-dimethylformamide (DMF) using Zn(CH3COO)2·2H2O (Zn(OAc)2·2H2O) as the Zn2+ source and H2S as the sulfur source catalyzed selective photoreduction of CO2 to HCOO- in the presence of triethylamine as an electron donor. When excess zinc acetate was added to the system, the efficiency increased while still keeping the product selectivity. The photocatalytic behavior of ZnS−DMF(OAc) is in contrast to that of ZnS−DMF(ClO4) prepared using Zn(ClO4)2·6H2O as the Zn2+ source, where both HCOO- and CO were produced, especially when excess zinc perchlorate was added into the system. FT-IR analysis of the ZnS−DMF(OAc) system revealed the presence of SH groups on the surface, explaining the gradual growth of the size with the addition of excess zinc acetate into the system. Extended X-ray absorption fine structure analysis revealed the correlation between the photocatalysis and the microscopic surface structure change of the ZnS nanocrystallites induced by the addition of Zn2+ to the nanocrystallite systems. The intimately interacting acetate ions to Zn atoms should prevent the formation of sulfur vacancies as catalytic sites of CO production, contributing to the enhanced photocatalytic activity for production of HCOO- due to the formation of the DMF-coordinated nanocrystallites.

In-situ Cd K-edge EXAFS analysis of colloidal CdS nanocrystallites (CdS-DMF, mean diameter 3.5 nm, hexagonal) prepared by reacting Cd2+ and H2S in N,N-dimethylformamide (DMF) was performed to clarify their microscopic surface structure in solution. The structure of the [Cd4(SC6H5)10]2- cluster (Cd4-cluster) in DMF was also examined. EXAFS analysis revealed that CdS-DMF is stabilized by solvation of the oxygen atoms of DMF to the cadmium atoms on the surface of CdS nanocrystallites as well as to Cd4-clusters in the solvent. The solvated surface structure of CdS nanocrystallites was affected by the addition of pentafluorothiophenol or H2S to the system. The correlation between the microscopic surface structure and optical properties of CdS nanocrystallites is discussed in terms of a model in which photogenerated carriers are trapped at lattice imperfections on the surface, i.e., surface vacancies.

Inhibitors of bromodomain and extraterminal domain (BET) proteins, a family of chromatin reader proteins, have therapeutic efficacy against various malignancies. However, the detailed mechanisms underlying the anti-tumor effects in distinct tumor types remain elusive. Here, we show a novel antitumor mechanism of BET inhibition in pancreatic ductal adenocarcinoma (PDAC). We found that JQ1, a BET inhibitor, decreased desmoplastic stroma, a hallmark of PDAC, and suppressed the growth of patient-derived tumor xenografts (PDX) of PDACs. In vivo antitumor effects of JQ1 were not always associated with the JQ1 sensitivity of respective PDAC cells, and were rather dependent on the suppression of tumor-promoting activity in cancer-associated fibroblasts (CAFs). JQ1 inhibited Hedgehog and TGF-β pathways as potent regulators of CAF activation and suppressed the expression of α-SMA, extracellular matrix, cytokines, and growth factors in human primary CAFs. Consistently, conditioned media (CM) from CAFs promoted the proliferation of PDAC cells along with the activation of ERK, AKT, and STAT3 pathways, though these effects were suppressed when CM from JQ1-treated CAFs was used. Mechanistically, chromatin immunoprecipitation experiments revealed that JQ1 reduced TGF-β–dependent gene expression by disrupting the recruitment of the transcriptional machinery containing BET proteins. Finally, combination therapy with gemcitabine plus JQ1 showed greater efficacy than gemcitabine monotherapy against PDAC in vivo. Thus, our results reveal BET proteins as the critical regulators of CAF-activation and also provide evidence that stromal remodeling by epigenetic modulators can be a novel therapeutic option for PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stromal reaction (desmoplasia). We have previously reported that mice with conditional Kras G12D mutation and knockout of TGF-β receptor type II ( Tgfbr2 ), PKF mice, develop PDAC with desmoplasia modulated by CXC chemokines that are produced by PDAC cells through tumor–stromal interaction. In this study, we further discovered that PDAC and cancer-associated fibroblast (CAF) accelerated each other’s invasion and migration through the CXC chemokines-receptor (CXCLs–CXCR2) axis. Heterozygous knockout of Cxcr2 in PKF mice (PKF2h mice) prolonged survival and inhibited both tumor angiogenesis and PDAC microinvasion. Infiltration of neutrophils, myeloid-derived suppressor cells (MDSCs), and arginase-1 + M2-like tumor-associated macrophages (TAMs) significantly decreased in the tumors of PKF2h mice, whereas inducible nitric oxide synthase (iNOS) + M1-like TAMs and apoptotic tumor cells markedly increased, which indicated that blockade of the CXCLs–CXCR2 axis resulted in a shift of immune-inflammatory microenvironment. These results suggest that blocking of the CXCLs–CXCR2 axis in tumor–stromal interactions could be a therapeutic approach against PDAC progression.

Periodontal tissue deteriorates under persistent oxidative stress induced by inflammatory reactions in the microflora of the oral cavity. This study aimed to evaluate the cellular properties of mouse gingival fibroblasts (MGFs) in the presence of oxidative stress. MGFs from 10-, 30- and 52-week-old mice were used to evaluate the changes in the cellular properties with aging. The study investigated the effects of oxidative stress on the cellular properties of MGFs from 10-week-old mice. The expression of p53, p21 and murine double minute 2 (Mdm2) in the MGFs in response to oxidative stress was also examined. By day 8, the number of MGFs increased in culture. However, the increase was markedly lower in MGFs derived from aged mice. Oxidative stress due to hydrogen peroxide (H2O2)-induced morphological changes characterized by a round shape with enlarged nuclei and expanded cytoplasm. The cell number of MGFs was decreased subsequent to treatment with 50 μM or a higher concentration of H2O2. MGFs treated with H2O2 at 20 μM showed a similar cell growth curve as the one seen in 52-week-old mice. Phosphorylated p53 protein was increased in MGFs subsequent to treatment with 20 μM H2O2, along with an upregulated transcription of p21 and Mdm2 mRNAs. These results suggest that treatment with a lower concentration of H2O2 in MGFs induces cell cycle arrest, resulting in stress-induced premature senescence, possibly correlated with the development of periodontal diseases.