Synthesis and structure-activity relationship studies of novel 3,9-substituted α-carboline derivatives with high cytotoxic activity against colorectal cancer cells

In our continued focus on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesized a novel series of 3,9-substituted α-carboline derivatives and evaluated the new compounds for antiproliferactive effects. Structure activity relationships revealed that a COOCH or CHOH group at position-3 and substituted benzyl group at position-9 of the α-carboline nucleus were crucial for maximal activity. The most active compound, , showed high levels of cytotoxicity against HL-60, COLO 205, Hep 3B, and H460 cells with IC values of 0.3, 0.49, 0.7, and 0.8 μM, respectively. The effect of compound on the cell cycle distribution demonstrated G2/M arrest in COLO 205 cells. Furthermore, mechanistic studies indicated that compound induced apoptosis by activating death receptor and mitochondria dependent apoptotic signaling pathways in COLO 205 cells. The new 3,9-substituted α-carboline derivatives exhibited excellent anti-proliferative activities, and compound can be used as a promising pro-apoptotic agent for future development of new antitumor agents

Assessing suitability of Co@Au core/shell nanoparticle geometry for improved theranostics in colon carcinoma

The interactions between cells and nanomaterials at the nanoscale play a pivotal role in controlling cellular behavior and ample evidence links cell intercommunication to nanomaterial size. However, little is known about the effect of nanomaterial geometry on cell behavior. To elucidate this and to extend the application in cancer theranostics, we have engineered core–shell cobalt–gold nanoparticles with spherical (Co@Au NPs) and elliptical morphology (Co@Au NEs). Our results show that owing to superparamagnetism, Co@Au NPs can generate hyperthermia upon magnetic field stimulation. In contrast, due to the geometric difference, Co@Au NEs can be optically excited to generate hyperthermia upon photostimulation and elevate the medium temperature to 45 °C. Both nanomaterial geometries can be employed as prospective contrast agents; however, at identical concentration, Co@Au NPs exhibited 4-fold higher cytotoxicity to L929 fibroblasts as compared to Co@Au NEs, confirming the effect of nanomaterial geometry on cell fate. Furthermore, photostimulation-generated hyperthermia prompted detachment of anti-cancer drug, Methotrexate (MTX), from Co@Au NEs-MTX complex and which triggered 90% decrease in SW620 colon carcinoma cell viability, confirming their application in cancer theranostics. The geometry-based perturbation of cell fate can have a profound impact on our understanding of interactions at nano-bio interface which can be exploited for engineering materials with optimized geometries for superior theranostic applications

Acupuncture Effects on Cardiac Functions Measured by Cardiac Magnetic Resonance Imaging in a Feline Model

The usefulness of acupuncture (AP) as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI), an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA) at bilateral acupoint Neiguan (PC6) on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI), including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology

Ecosystem-Driven Design of In-Home Terminals Based on Open Platform for the

Abstract—In-home healthcare services based on the Internet-of-Things (IoT) have great business potentials. To turn it into reality, a business ecosystem should be established first. Technical solutions should therefore aim for a cooperative ecosystem by meeting the interoperability, security, and system integration requirements. In this paper, we propose an ecosystem-driven design strategy and apply it in the design of an open-platform-based in-home healthcare terminal. A cooperative business ecosystem is formulated by merging the traditiona

Printed Nanostructures for Organic Photovoltaic Cells and Solution‐Processed Polymer Light‐Emitting Diodes

We review the progress on printing‐based technologies for organic electronic devices, especially organic photovoltaic (OPV) cells and polymer light‐emitting diodes (PLEDs). First we discuss recent efforts to introduce interdigitated nanostructures on the order of tens of nanometers to the photoactive layers of OPV cells using nanoimprint lithography including a soft‐printing process developed in our research group that can easily produce sub‐20 nm scale organic semiconductor nanopillars. Second, we review solution‐processible printing technologies such as gravure printing, screen printing, blade coating, and slot–die coating for high‐throughput manufacturing of PLEDs.Illuminating results: This article reviews the progress on printing‐based technologies for organic electronic devices, especially organic photovoltaic (OPV) cells and polymer light‐emitting diodes (PLEDs), including solution‐processible printing technologies such as gravure printing, screen printing, blade coating, and slot–die coating for high‐throughput manufacturing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111088/1/340_ftp.pd

Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression

Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity

One-Step UV-Induced Synthesis of Polypyrrole/Ag Nanocomposites at the Water/Ionic Liquid Interface

Polpyrrole (PPy)/Ag nanocomposites were successfully synthesized at the interface of water and ionic liquid by one-step UV-induced polymerization. Highly dispersed PPy/Ag nanoparticles were obtained by controlling the experimental conditions. The results of Fourier-transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy revealed that the UV-induced interface polymerization leaded to the formation of PPy incorporating silver nanoparticles. It was also found that the electrical conductivity of PPy/Ag nanocomposite was about 100 times higher than that of pure PPy

Diversification of importin-α isoforms in cellular trafficking and disease states.

The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases