Publications by authors named "Takayuki Mizutani"

Functional disorders of the thyroid remain a global challenge and have profound impacts on human health. Serving as the barometer for thyroid function, thyroid-stimulating hormone (TSH) is considered the single most useful test of thyroid function. However, the prevailing TSH immunoassays rely on two types of antibodies in a sandwich format.

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While immunoassays are pivotal to medical diagnosis and bioanalytical chemistry, the current landscape of public health has catalyzed an important shift in the requirements of immunoassays that demand innovative solutions. For example, rapid, label-free, and low-cost screening of a given analyte is required to inform the best countermeasures to combat infectious diseases in a timely manner. Yet, the current design of immunoassays cannot accommodate such requirements as constraint by accumulative challenges, such as repeated incubation and washing, and the need of two types of antibodies in the sandwich format.

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Small molecules play a pivotal role in regulating physiological processes and serve as biomarkers to uncover pathological conditions and the effects of therapeutic treatments. However, it remains a significant challenge to detect small molecules given the size as compared to macromolecules. Recently, the newly emerging plasmonic immunoassays based on surface-enhanced Raman scattering (SERS) offer great promise to deliver extraordinary sensitivity.

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Enhancing light-matter interactions is fundamental to the advancement of nanophotonics and optoelectronics. Yet, light diffraction on dielectric platforms and energy loss on plasmonic metallic systems present an undesirable trade-off between coherent energy exchange and incoherent energy damping. Through judicious structural design, both light confinement and energy loss issues could be potentially and simultaneously addressed by creating bound states in the continuum (BICs) where light is ideally decoupled from the radiative continuum.

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MicroRNAs (miRNAs) serve important roles in regulating various physiological activities through RNA interference (RNAi). miR-122 is an important mediator of RNAi that is known to control hepatitis C virus (HCV) replication and is being investigated in clinical trials as a target for anti-HCV therapy. In this study, we developed novel oligonucleotides containing non-nucleotide residues, termed iMIRs, and tested their abilities to inhibit miR-122 function.

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Small interfering RNA (siRNA)-based therapeutics have been used in humans and offer distinct advantages over traditional therapies. However, previous investigations have shown that there are several technical obstacles that need to be overcome before routine clinical applications are used. Currently, we are launching a novel class of RNAi therapeutic agents (PnkRNA™, nkRNA) that show high resistance to degradation and are less immunogenic, less cytotoxic, and capable of efficient intracellular delivery.

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Background: Although identification of the target mRNAs of micro RNAs (miRNAs) is essential to understanding their function, the low complementarity between miRNAs and their target mRNAs has complicated this process. In this study, we sought to identify miRNAs which reduce the expression of the transcription factor Zeb-2, a transcriptional repressor of E-cadherin which is known to be down regulated by members of the miR-200 family (miR-200a,b,c miR-429, and miR-141).

Findings: We first used a computational target predicting system to identify 82 candidate miRNAs which bound the 3'UTR region of the Zeb-2 mRNA.

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Despite the therapeutic potential of nucleic acid drugs, their clinical application has been limited in part by a lack of appropriate delivery systems. Exosomes or microvesicles are small endosomally derived vesicles that are secreted by a variety of cell types and tissues. Here, we show that exosomes can efficiently deliver microRNA (miRNA) to epidermal growth factor receptor (EGFR)-expressing breast cancer cells.

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RNA interference (RNAi) is being widely used in functional gene research and is an important tool for drug discovery. However, canonical double-stranded short interfering RNAs are unstable and induce undesirable adverse effects, and thus there is no currently RNAi-based therapy in the clinic. We have developed a novel class of RNAi agents, and evaluated their effectiveness in vitro and in mouse models of acute lung injury (ALI) and pulmonary fibrosis.

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We report the construction and application of a mammalian genome-wide RNAi library. The oligodeoxynucleotides encoding approximately 200,000 shRNA sequences that targeted 47,400 human transcripts were inserted into a lentivirus vector pFIV-H1-puro, and a pool of pseudovirus particles with a complexity of approximately 200,000 were used to infect target cells. From the cells surviving apoptogenic Fas stimulation, four candidate shRNA sequences were obtained that provided resistance to Fas-induced cell death, including two shRNAs for caspase-8, an shRNA for Bid, and an shRNA for Fas.

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We identified that microRNA expression changed dynamically during liver development and found that miR-500 is an oncofetal miRNA in liver cancer. miR-500 was abundantly expressed in several human liver cancer cell lines and 45% of human hepatocellular carcinoma (HCC) tissue. Most importantly, an increased amount of miR-500 was found in the sera of the HCC patients.

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In this study, in addition to the karyotype analysis, the chromosomal distributions of 5 S and 18 S rDNAs, and the Arabidopsis-type (T3AG3) telomeric sequences were detected by means of fluorescence in situ hybridization (FISH) to promote the information of chromosomal organization and evolution in the cultivated lettuce and its wild relatives, L. sativa, L. serriola, L.

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Random amplified polymorphic DNA (RAPD) analysis was used to determine the genetic relationships among seventeen species of the Acanthopanax species. The DNA isolated from the leaves of the samples was used as template in polymerase chain reaction (PCR) with twenty random decamer primers in order to distinguish plant subspecies at the level of their genomes. The RAPD patterns were compared by calculating pairwise distances using Dice similarity index, and produced to the genetic similarity dendrogram by unweighted pair-group method arithmetic averaged (UPGMA) analysis, showing three groups; a major cluster(twelve species), minor cluster (4 species) and single-clustering species.

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