Gas-Phase Synthesis for Label-Free Biosensors: Zinc-Oxide Nanowires Functionalized with Gold Nanoparticles.

Metal oxide semiconductor nanowires have important applications in label-free biosensing due to their ease of fabrication and ultralow detection limits. Typically, chemical functionalization of the oxide surface is necessary for specific biological analyte detection. We instead demonstrate the use of gas-phase synthesis of gold nanoparticles (Au NPs) to decorate zinc oxide nanowire (ZnO NW) devices for biosensing applications. Uniform ZnO NW devices were fabricated using a vapor-solid-liquid method in a chemical vapor deposition (CVD) furnace. Magnetron-sputtering of a Au target combined with a quadrupole mass filter for cluster size selection was used to deposit Au NPs on the ZnO NWs. Without additional functionalization, we electrically detect DNA binding on the nanowire at sub-nanomolar concentrations and visualize individual DNA strands using atomic force microscopy (AFM). By attaching a DNA aptamer for streptavidin to the biosensor, we detect both streptavidin and the complementary DNA strand at sub-nanomolar concentrations. Au NP decoration also enables sub-nanomolar DNA detection in passivated ZnO NWs that are resilient to dissolution in aqueous solutions. This novel method of biosensor functionalization can be applied to many semiconductor materials for highly sensitive and label-free detection of a wide range of biomolecules.

miR-141 Inhibits Proliferation and Migration of Colorectal Cancer SW480 Cells.

BACKGROUND: This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). MATERIALS AND METHODS: SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence. Transwell assay was conducted to determine the migration rates of cells. Subcutaneous xenograft models were used to examine the effect of miR-141 on tumorigenicity. Human mitogen-activated protein kinase (MAPK) and receptor tyrosine kinase (RTK) pathway phosphorylation array assays were used to interrogate MAPK and RTK pathway activation. RESULTS: miR-141 directly targeted zinc finger E-box-binding homeobox 1/2 (ZEB1/2). We first determined the expression levels of ZEB1 and ZEB2 in miR-141-expressing cells and miR-141-knockdown cells and found that inhibition of miR-141 significantly increased the expression of ZEB2. In vitro study revealed that miR-141 overexpression inhibited the expression of Ki-67. Furthermore, overexpression of miR-141 led to a significant reduction in the proliferation of SW480 cells via induction of cell-cycle arrest at the G1 stage. In contrast, inhibition of miR-141 markedly promoted the proliferation of SW480 cells by promoting cell-cycle progression. Moreover, overexpression of miR-141 significantly inhibited SW480 cell migration in vitro. In addition, overexpression of miR-141 significantly reduced tumor size and weight, and inhibited the growth of SW480 cell-derived tumor in nude mice. Notably, overexpression of miR-141 also suppressed the liver metastasis of SW480 cells in nude mice. Using RTK and MAPK arrays, we found increased phosphorylation of hepatocyte growth factor receptor (HGFR/c-MET) following inhibition of miR-141, but phosphorylation of P53, AKT, ERK1/2, P38 and mTOR, etc., in SW480 cells was not affected by miR-141. CONCLUSION: Our results suggest that miR-141 functions as a tumor suppressor through ZEB2 and HGFR in CRC cells.

Honokiol: a non-adipogenic PPARγ agonist from nature.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators. METHODS: We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists. RESULTS: The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain. CONCLUSION: We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo. GENERAL SIGNIFICANCE: This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine.

Radical and local excisional methods of sphincter-sparing surgery after high-dose radiation for cancer of the distal 3 cm of the rectum.

BACKGROUND: Despite conventional attitudes that interdict sphincter-preservation surgery (SPS) for cancers arising in the terminal 3 cm of rectum, we have selectively employed high-dose preoperative external radiation (HDPER) and either radical or local excisional SPS techniques for rectal cancer arising between the 0.5 and 3 cm levels above the anorectal ring. We have reported a preliminary experience with HDPER and full-thickness local excision (FTLE) and three different methods of radical SPS. We now describe our experience with a single method of radical excision, transanal abdominal transanal proctosigmoidectomy with coloanal anastomosis (TATA) and FTLE in conjunction with HDPER for cancers of the distal 3 cm of rectum based on specific guidelines. METHODS: Since 1984, 109 patients with cancers at or below the 3 cm level have been treated with HDPER in doses of 4,500-7,000 cGy and a sphincter-preserving radical or local excision method in a prospective rectal cancer management program. Sixty-five patients (group A) underwent transanal abdominal transanal radical proctosigmoidectomy with colonal anastomosis (TATA) and 44 patients (group B) underwent FTLE. RESULTS: There was one death (1%). Mean follow-up was 40 months. Local recurrence rates for groups A and B were 9 and 14%, respectively. Kaplan-Meier 5-year actuarial survival was 85 and 90% for groups A and B, respectively, and 87% collectively. CONCLUSION: Experience with 109 patients with cancers of the distal 3 cm of rectum indicates that SPS can be accomplished by either radical or local excisional methods with acceptable local control and survival if HDPER and strict selection guidelines are employed.

Prolactin secretion in alcoholics. / Prolactin secretion in alcoholic patients

Se determinaron los niveles de prolactina circulante en condiciones basales y la respuesta de la misma a estimulacion con tiroliberina, en un grupo de 22 pacientes alcoholicos y un grupo de sujetos sanos con caracteristicas demograficas similares El objetivo fue establecer los efectos del consumo cronico y excesivo de alcohol sobre la secrecion de prolactina por la hipofisis. Los pacientes fueron estudiados tres semana despues de haber cesado su ingestion de alcohol. Los resultados sugieren, que el consumo exagerado de alcohol por si mismo no tiene efectos permanentes en la secrecion de prolactina ni en la respuesta a tiroliberina, aun cuando en algunos pacientes se encontraron valores ligeramente menores que en sus controles.Los autores discuten la importancia que tienen las alteraciones hepaticas de causas diversas en la secrecion de prolactina asi como las diferencias y similitudes de los datos aqui descritos con otros reportados en la literatura