I. Selim Bey’in ikinci kısım Amerika hatıraları

I. Selim Bey'in Haftalık Mecmua'da tefrika edilen I. Selim Bey’in İkinci Kısım Amerika Hatıraları adlı roman

Cytotoxic Alkaloids from <i>Fusarium incarnatum</i> Associated with the Mangrove Tree <i>Aegiceras corniculatum</i>

Several unusual alkaloids, <i>N</i>-2-methylpropyl-2-methylbutenamide (<b>1</b>), 2-acetyl-1,2,3,4-tetrahydro-β-carboline (<b>2</b>), fusarine (<b>3</b>), fusamine (<b>4</b>), and 3-(1-aminoethylidene)-6-methyl-2<i>H</i>-pyran-2,4­(3<i>H</i>)-dione (<b>5</b>), were isolated from the culture broth of <i>Fusarium incarnatum</i> (HKI0504), an endophytic fungus of the mangrove plant <i>Aegiceras corniculatum</i>. Compounds <b>2</b>, <b>4</b>, and <b>5</b> exhibit weak antiproliferative and cytotoxic activities against HUVEC, K-562, and HeLa human cell lines, respectively

Nonfouling Property of Zwitterionic Cysteine Surface

Applications of implantable bioelectronics for analytical and curative purposes are currently limited by their poor long-term biofunctionality in physiological media and nonspecific interactions with biomolecules. In an attempt to prolong in vivo functionality, recent advances in surface modifications have demonstrated that zwitterionic coatings can rival the performance of conventional poly­(ethylene glycol) polymers in reducing nonspecific protein fouling. Herein, we report the fabrication of a very thin layer of nonfouling zwitterionic cysteine surface capable of protecting implantable bioelectronics from nonspecific adsorption of plasma proteins. This work is the first of its kind to fabricate, through solution chemistry, a cysteine surface exhibiting zwitterionic state as high as 88% and to demonstrate antibiofouling under the exposure of bovine serum albumin (BSA) and human serum. The fabricated surface utilized a minimal amount of gold substrate, approximately 10 nm, and an extremely thin antifouling layer at 1.14 nm verified by ellipsometry. X-ray photoelectron spectroscopy assessment of the nitrogen (N_1s) and carbon (C_1s) spectra conclude that 87.8% of the fabricated cysteine surface is zwitterionic, 2.5% is positively charged, and 9.6% is noncharged. Antibiofouling performance of the cysteine surface is quantitatively determined by bicinchoninic acid (BCA) protein assay as well as qualitatively confirmed using scanning electron spectroscopy. Cysteine surfaces demonstrated a BSA fouling of 3.9 ± 4.84% μg/cm², which is 93.6% and 98.5% lower than stainless steel and gold surfaces, respectively. Surface plasmon resonance imaging analysis returned similar results and suggest that a thinner cysteine coating will enhance performance. Scanning electron microscopy confirmed the results of BCA assay and suggested that the cysteine surface demonstrated a 69% reduction to serum fouling. The results reported in this paper demonstrate that it is possible to achieve a highly zwitterionic surface through solution chemistry on a macroscopic level that is capable of improving biocompatibility of long-term implantable bioelectronics

STAT5 is involved in antiestrogen-induced Cyclin D1 promoter activity.

<p>(A). The involvement of STAT5 in antiestrogens-induced Cyclin D1 promoter activity. Cells were transfected with the luciferase reported plasmid Cyclin D1 pl-963 together with an empty expression vector or two dominant-negative STAT5a mutants, STAT5aΔ713 and STAT5aΔ740, respectively. Transfected cells were treated with vehicle (ethanol), 1 nM or 5 µM of antiestrogens. Columns: means of the relative luciferase activity from four independent experiments. Luciferase activity in the cells transfected with an empty expression vector and treated with vehicle is arbitrarily set as 1.0; bars, SE. *, p<0.05, for cells treated with vehicle (V) vs 1 nM of antiestrogens. (B). The GAS1 is involved in induction of the Cyclin D1 promoter activity by antiestrogens. Cells were transiently transfected with either the wild-type Cyclin D1 promoter (CycD1) or the same promoter construct containing mutated GAS1 (GAS1mut) or GAS2 (GAS2mut) sequence, respectively. Transfected cells were treated with vehicle or 1 nM of antiestrogens, and the luciferase activity was presented relative to the wild-type Cyclin D1 promoter-transfected cells treated with vehicle that is arbitrarily set as 1.0. *, p<0.05, for cells treated with vehicle (V) vs 1 nM of antiestrogens.</p

Different concentrations of antiestrogens affect the association of ER-α36 and Src differently.

<p>Co-immunoprecipitation and Western blot analysis of HA-ER-α36 and Src in MDA-MB-231 cells. Cells transiently transfected with an expression of HA-tagged ER-α36 and treated with different concentrations of antiestrogens for 10 min were lysised and the cell lysates were immunoprecipitated with pre-immune and anti-HA antibodies. The immunoprecipitates were blotted by anti-HA and anti-Src antibodies.</p

Src is involved in antiestrogen-induced Cyclin D1 expression.

<p>(A). Western blot analysis of Cyclin D1 expression in MDA-MB-231 and -436 cells. Cells were treated with vehicle (ethanol) and antiestrogens alone or together with the Src inhibitors PP2 and dasatinib, the EGFR inhibitor AG1478 and PI3K inhibitor LY294002. Cell lysates were analyzed with anti-Cyclin D1 antibody and anti-Acin antibody was used to ensure equal loading. The experiment was repeated three times, and the representative results are shown. (B). Src inhibitors inhibit antiestrogen-induced Cyclin D1 promoter activity. ER-negative breast cancer cells were transfected with the luciferase reported plasmid Cyclin D1 pl-963 that containing a luciferase gene driven by the Cyclin D1 promoter. Transfected cells were treated with vehicle (ethanol), 1 nM or 5 µM of antiestrogens, and 1 nM of antiestrogens together with different inhibitors. The luciferase activities were assayed and normalized using a cytomegalovirus promoter-driven Renilla luciferase plasmid. Columns: means of the relative luciferase activity in cells treated with vehicle that is arbitrarily set as 1.0 from four independent experiments; bars, SE. *, p<0.05, for cells treated with vehicle (V) vs 1 nM of antiestrogens, or vehicle (V) vs 1 nM of antiestrogens plus AG1478. (C). The involvement of Src in antiestrogen-induced Cyclin D1 promoter activity. Cells were transfected with the luciferase reported plasmid Cyclin D1 pl-963 together with an empty expression vector or Src mutants, a dominant-negative mutant (SrcK295R) and a constitutively active mutant (SrcY527F). Transfected cells were treated with vehicle (ethanol), 1 nM or 5 µM of antiestrogens. The luciferase activities were assayed and normalized using a cytomegalovirus-driven Renilla luciferase plasmid. Columns: means of the relative luciferase activity from four independent experiments. Luciferase activity in transfected cells treated with vehicle is arbitrarily set as 1.0; bars, SE. *, p<0.05, for cells treated with vehicle (V) vs 1 nM of antiestrogens. #, p<0.05, for cells treated with vehicle (V) vs 5 µM of antiestrogens.</p

Antiestrogens induce biphasic STAT5 activities in ER-negative breast cancer cells.

<p>(A). ER-negative breast cancer cells were transfected with the luciferase reported plasmid 4XM67 TATA-TK-Luc that containing four copies of STAT-binding sites upstream of the minimal TK promoter. Transfected cells were treated with vehicle (ethanol), 1 nM or 5 µM of 4-OHT or ICI 182, 780. The luciferase activities were assayed and normalized using a cytomegalovirus-driven Renilla luciferase plasmid. Columns: means of the relative luciferase activity from four independent experiments. Luciferase activity in transfected cells treated with vehicle is arbitrarily set as 1.0; bars, SE. *, p<0.05, for cells treated with vehicle (V) vs 1 nM of antiestrogens. #, p<0.05, for cells treated with 5 µM vs 1 nM of antiestrogens. (B&C). Cells were transfected with the 4XM67 TATA-TK-Luc reporter together with an empty expression vector (vector) and the expression vectors of two dominant-negative STAT5a mutants carrying truncations at their C-terminal (STAT5aΔ713 and STAT5aΔ740) before treated with vehicle (ethanol), 1 nM or 5 µM of antiestrogens. Columns: means of the relative luciferase activity from three independent experiments. Luciferase activity of cells co-transfected with an empty expression vector and treated with vehicle is arbitrarily set as 1.0; bars, SE. *, p<0.05, for cells treated with vehicle (V) vs 1 nM of antiestrogens.</p

ER-negative breast cancer cells exhibit biphasic antistrogen signaling.

<p>(A). The effects of 4-OHT and ICI 182, 780 on the proliferation rate of MDA-MB-231 and MDA-MB-436 cells. Cells maintained for three days in phenol red-free DMEM plus 2.5% dextran-charcoal-stripped fetal calf serum were treated with indicated concentrations of 4-OHT, ICI or ethanol vehicle as a control. The cell numbers were determined using an automatic cell counter after 12 days. Five dishes were used for each concentration and experiments were repeated more than three times. The mean cell number ± SE are shown. (B). The dose-dependent phosphorylation pattern of the MAPK/ERK1/2 in MDA-MB-231 and MDA-MB-436 cells treated with different concentrations of antiestrogens. Starved cells were treated with indicated doses of 4-OHT or ICI 182, 780 (ICI) for 10 min. Western blot analysis was performed to assess induction of ERK1/2 phosphorylation. The experiment was repeated more than three times. The representative results are shown. (C). The dose dependent induction Cyclin D1 by antiestrogens in MDA-MB-231 and MDA-MB-436 cells. The experiment was repeated more than three times. The representative results are shown.</p

OPN protein localization in the CRC and its liver metastasis visualized by immunohistochemistry. a

<p>In <i>IHC</i>, OPN proteins (brown positive stain) were localized in cytoplasm of CRC cells in primary lesions(x200). <b>b</b> Adjacent normal colorectal tissues were negative(x200). <b>c</b> Positive stain was found both in CRC cells and adjacent normal hepatocytes in liver metastatic tissues(x100). <b>d</b> As controls, OPN proteins stain in normal liver tissues without CRC metastasis was negative(x100).</p

Expression of integrin αv and CD44v6 in normal hepatocytes with Immunohistochemistry. a,

<p>In <i>IHC</i>, integrin αv proteins (brown positive stain) were localized in cytoplasm of hepatocytes (×400). <b>b,</b> CD44v6 proteins (brown positive stain) were localized in cytoplasm of hepatocytes (×400).</p