Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells

Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.     

Attenuating Effects of Dieckol on Hypertensive Nephropathy in Spontaneously Hypertensive Rats

Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)/TGFβ/SMAD, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R/TGFβ/SMAD was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R/TGFβ/SMAD, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.     

Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.     

Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.     

Material Design for 3D Multifunctional Hydrogel Structure Preparation

Hydrogels are recognized as one of the most promising materials for e-skin devices because of their unique applicable functionalities such as flexibility, stretchability, biocompatibility, and conductivity. Beyond the excellent sensing functionalities, the e-skin devices further need to secure a target-oriented 3D structure to be applied onto various body parts having complex 3D shapes. However, most e-skin devices are still fabricated in simple 2D film-type devices, and it is an intriguing issue to fabricate complex 3D e-skin devices resembling target body parts via 3D printing. Here, a material design guideline is provided to prepare multifunctional hydrogels and their target-oriented 3D structures based on extrusion-based 3D printing. The material design parameters to realize target-oriented 3D structures via 3D printing are systematically derived from the correlation between material design of hydrogels and their gelation characteristics, rheological properties, and 3D printing processability for extrusion-based 3D printing. Based on the suggested material design window, ion conductive self-healable hydrogels are designed and successfully applied to extrusion-based 3D printing to realize various 3D shapes.     

Fabrication of Biodegradable Polyurethane Foam Scaffolds with Customized Shapes and Controlled Mechanical Properties by Gas Foaming Technique

Poly(ε-caprolactone) (PCL)-based polyurethane (PU) foam scaffolds with different mechanical properties are fabricated using a gas foaming technique to use as porous substitutes for ear or bone with cartilage. PCL diol or triol is used as a polyol in PU foam for biocompatibility and biodegradation, with an aqueous gelatin solution as a blowing agent. The highly porous inner and outer structures of the scaffolds are developed by employing a silicone surfactant and sulfuric acid, respectively. The PU scaffolds prepared by PCL diol show ductile and flexible properties, whereas the PU scaffolds prepared by PCL triol exhibit high compression strength. In vitro test reveals the low toxicity of the PU scaffolds and the high ALP activity of MC3T3-E1 cells in the PU scaffold prepared by PCL triol. By taking advantage of the difference in mechanical properties, customized PU scaffolds with ear or bone shapes are fabricated using a silicone mold. The PU scaffolds with two compartments of PCL diol and triol (corresponding to cartilage and bone, respectively) are fabricated as a substitute for bone with cartilage. It is believed that the PU scaffolds with highly porous structure and controlled mechanical properties have wide potential application for tissue engineering.     

Facile Deposition of Silver Nanoparticles on Photonic Cellulose Nanocrystals Films: A Study on Solvent Stability and Post Antibacterial Activity

Cellulose nanocrystals (CNCs) incorporated with silver nanoparticles (AgNPs) photonic films have drawn considerable attention due to their plasmonic chiroptical activity. However, the exploitation of some fundamental properties for practical use such as the affinity analysis of metal nanoparticles attached to the surface of photonic films according to the solvent compatibility and antibacterial activity under physical conditions has yet not been studied. Hence, a facile process of in situ deposition of AgNPs into the chiral structure of CNC films is proposed. CNC photonic films, cross-linked by glutaraldehyde are prepared. This interaction generated the solvents-stable photonic film with a considerable amount of unreacted aldehyde functional groups that facilitates the reduction of Ag salt to AgNPs. The formed AgNPs in the photonic films show excellent stability over immersion in various polar and non-polar solvents. The post-solvent treated photonic films display excellent contact-based antibacterial behavior against gram-negative Escherichia coli.     

An experimental evaluation of the effects of ripple current generated by the power conditioning stage on a proton exchange membrane fuel cell stack

In this article, an impedance model of the proton exchange membrane fuel cell stack (PEMFCS) is proposed. The proposed study employs an equivalent circuit of the PEMFCS derived by the frequency response analysis technique. An equivalent circuit for the PEMFCS is developed to evaluate the effects of ripple currents generated by the power-conditioning unit. The calculated results are then verified by means of experiments using a commercially available PEMFCS. The relationship between ripple current and fuel cell performance, such as power loss and fuel consumption, is investigated. Experimental results show that the ripple current can contribute up to a 6% reduction in the available output power. This paper was presented at the Fuel Cells: Materials, Processing, and Manufacturing Technologies Symposium sponsored by the Energy/Utilities Industrial Sector & Ground Transportation Industrial Sector and the Specialty Materials Critical Technologies Sector at the ASM International Materials Solutions Conference, October 13–15, 2003, in Pittsburgh, PA. The symposium was organized by P. Singh, Pacific Northwest National Laboratory, S.C. Deevi, Philip Morris USA, T. Armstrong, Oak Ridge National Laboratory, and T. Dubois, U.S. Army CECOM.     

Shear strength and aging characteristics of 63Sn−37Pb solder bumps with various solder ball and pad sizes

The shear strength and aging characteristics of 63Sn–37Pb solder bumps were characterized with variation in solder ball and UBM pad sizes. The shear strength increased with shorter effective crack size,a _effs which was determined with the solder ball and pad sizes. The shear strength of the solder bumps on Au/Ni/Cu and Ni/Cu did not change significantly with reflow time. Substantial decrease in the shear strength occurred for the solder bumps formed on Au/Ni/Cu with aging treatment, and the shear strength after aging was also related to the bump shape which was determined with the solder ball and pad sizes.