Dual Silencing of Hsp27 and c-FLIP Enhances Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells

We evaluated effect of dual gene silencing of Hsp27 and c-FLIP in doxazosin-induced apoptosis of PC-3 cell. After transfection using Hsp27 and c-FLIP siRNA mixture (dual silencing), doxazosin treatment was done at the concentrations of 1, 10, and 25 μM. We checked apoptosis of PC-3 cells with and TUNEL staining. We also checked interaction between Hsp27 and C-FLIP in the process of apoptosis inhibition. Spontaneous apoptotic index was 5% under single gene silencing of Hsp27 and c-FLIP and 7% under dual silencing of Hsp27 and c-FLIP. When doxazosin treatment was added, apoptotic indices increased in a dose-dependent manner (1, 10, and 25 μM): nonsilencing 10, 27, and 52%; Hsp27-silencing: 14, 35, and 68%; c-FLIP silencing: 21, 46, and 78%; dual silencing: 38, 76, and 92%. While c-FLIP gene expression decreased in Hsp27- silenced cells, Hsp27 gene expression showed markedly decreased pattern in the cells of c-FLIP silencing. The knockout of c-FLIP and Hsp27 genes together enhances apoptosis even under 1 μM, rather than low concentration, of doxazosin in PC-3 cells. This finding suggests a new strategy of multiple knockout of antiapoptotic and survival factors in the treatment of late-stage prostate cancer refractory to conventional therapy

National representative analysis of unilateral hearing loss and hearing aid usage in South Korea.

A definitive study on the prevalence of adult unilateral hearing loss and hearing aid rehabilitation is lacking in Korea. The purpose of our study was to investigate the prevalence of adult unilateral hearing loss and the factors associated with hearing aid use in patients with unilateral hearing loss in South Korea. We obtained data from 2009 to 2012 from the Korea National Health and Nutrition Examination Surveys (KNHANES), a cross-sectional, nationwide and population-based survey in the Republic of Korea. We analyzed the prevalence and associated factors of unilateral hearing loss and hearing aid adoption by univariable and multivariable analysis. Unilateral hearing loss was defined as pure tone average ≥ 41 dB in the worse hearing ear, and < 41 dB in the other ear assessed at 0.5, 1.0, 2.0, and 3.0 kHz. From 2009 to 2012, 33,252 individuals participated in the KNHANES. Among them, the number of patients with unilateral hearing loss was 1632 (5.55%) and the prevalence of hearing aid adoption in unilateral hearing loss was 1.56%. We also compared the factors between hearing aid users and non-users. Occupational status (OR 3.759, 95% CI 1.443-9.804), the hearing threshold in the better ear (OR 1.088, 95% CI 1.029-1.151), and hearing threshold in the worse ear (OR 1.031, 1.005-1.058) were found to affect the adoption of hearing aids. The prevalence of noise exposure at work in hearing aid users was significantly lower than the prevalence of noise exposure at work in those with no hearing aid. The prevalence of hearing aid use in patients with unilateral hearing loss in Korea is very low compared to other countries. Public health education is needed to increase public awareness of unilateral hearing loss, hearing aid adoption and its continued usage. Auditory rehabilitation should be actively recommended to patients with unilateral hearing loss

Ligand Coupling and Decoupling Modulates Stem Cell Fate

In natural microenvironment, various proteins containing adhesive ligands in fibrous and non-fibrous structures dynamically couple and decouple to regulate stem cell fate. Herein, materials presenting movably couplable ligands are developed by grafting liganded gold nanoparticles (AuNPs) to a substrate followed by flexibly grafting liganded movable linear nanomaterials (MLNs) to the substrate via a long bendable linker, thereby creating a space between the MLNs and the AuNPs in the decoupled state. Magnetic control of the MLNs decreases this space via the bending of the linker to couple the MLNs to the AuNPs. Remote control of ligand coupling stimulates integrin recruitment to the coupled ligands, thereby non-toxically facilitating the focal adhesion, mechanosensing, and potential differentiation of stem cells, which is suppressed by ligand decoupling. Versatile tuning of size, aspect ratio, distributions, and ligands of the MLNs can help to decipher dynamic ligand-coupling-dependent stem cell fate to advance regenerative therapies.11Nsciescopu

Modulation of Macrophages by In Situ Ligand Bridging

Extracellular matrix (ECM) proteins containing cell-attachable Arg-Gly-Asp (RGD) sequences exhibit variable bridging and non-bridging in fibronectin-collagen and laminin-collagen complexes that can regulate inflammation, tissue repair, and wound healing. In this study, linking molecule-mediated conjugation of 1D magnetic nanocylinders (MNCs) to material surfaces pre-decorated with gold nanospheres (GNSs) is performed, thereby yielding RGD-coated MNCs (RGD-MNCs) over RGD-coated GNSs (RGD-GNSs) in a non-bridging state. The RGD-MNCs are drawn closer to the RGD-GNSs via magnetic field-mediated compression of the linking molecules to establish the bridging between them. Relative proportion of the RGD-MNCs to the RGD-GNSs is optimized to yield effective remote stimulation of integrin binding to variably bridged RGDs similar to that of invariably bridged RGDs used as a control group. Remote manipulation of the RGD bridging facilitates the attachment structure assembly of macrophages that leads to pro-healing/anti-inflammatory phenotype acquisition. In contrast, the non-bridged RGDs inhibited macrophage attachment that acquired pro-inflammatory phenotypes. The use of various nanomaterials in constructing heterogeneous RGD-coated materials can further offer various modes in remote switching of RGD bridging and non-bridging to understand dynamic integrin-mediated modulation of macrophages that regulate immunomodulatory responses, such as foreign body responses, tissue repair, and wound healing