Kamigyō-ku, Japan
Kamigyō-ku, Japan

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Kong Y.-J.,Nanjing Medical University | Yi H.-G.,Nanjing Medical University | Dai J.-C.,Nanjing Medical University | Wei M.-X.,Nanjing Medical University | And 2 more authors.
World Journal of Gastroenterology | Year: 2014

Aim: To systematically review pathological changes of gastric mucosa in gastric atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori) eradication. Methods: A systematic search was made of PubMed, Web of Science, EMBASE, ClinicalTrials.gov, OVID and the Cochran Library databases for articles published before March 2013 pertaining to H. pylori and gastric premalignant lesions. Relevant outcomes from articles included in the meta-analysis were combined using Review Manager 5.2 software. A Begg's test was applied to test for publication bias using STATA 11 software. χ 2 and I 2 analyses were used to assess heterogeneity. Analysis of data with no heterogeneity (P > 0.1, I 2 < 25%) was carried out with a fixed effects model, otherwise the causes of heterogeneity were first analyzed and then a random effects model was applied. Results: The results of the meta-analysis showed that the pooled weighted mean difference (WMD) with 95%CI was 0.23 (0.18-0.29) between eradication and non-eradication of H. pylori infection in antral IM with a significant overall effect (Z = 8.19; P <0.00001) and no significant heterogeneity (χ 2 = 27.54, I 2 = 16%). The pooled WMD with 95%CI was -0.01 (-0.04-0.02) for IM in the corpus with no overall effect (Z = 0.66) or heterogeneity (χ 2 = 14.87, I 2 =0%) (fixed effects model). In antral GA, the pooled WMD with 95% CI was 0.25 (0.15-0.35) with a significant overall effect (Z = 4.78; P < 0.00001) and significant heterogeneity (χ 2 = 86.12, I 2 = 71%; P < 0.00001). The pooled WMD with 95% CI for GA of the corpus was 0.14 (0.04-0.24) with a significant overall effect (Z = 2.67; P = 0.008) and significant heterogeneity (χ 2 = 44.79, I 2 = 62%; P = 0.0003) (random effects model). Conclusion: H. pylori eradication strongly correlates with improvement in IM in the antrum and GA in the corpus and antrum of the stomach. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Hirata A.,HiPep Laboratories | Nokihara K.,HiPep Laboratories | Kawamoto Y.,Kyoto University | Bando T.,Kyoto University | And 5 more authors.
Journal of the American Chemical Society | Year: 2014

A polyamide containing N-methylpyrrole (Py) and N-methylimidazole (Im), designated PIPA, binds with high affinity and specificity to specific nucleotide sequences in the minor groove of double-helical DNA. Based on a recent report of the synthesis of PIPA for telomere visualization, the present paper focused on the size of the connecting part (hinge region) of two PIPA segments of the tandem hairpin PIPA, Dab(Im-Im-Py)-Py-Py-Py-Im-[Hinge]-Dab(Im-Im-Py)-Py-Py-Py- Im-βAla-NH(CH2)3N(CH3)-(CH 2)3NH-[Dye]. The present paper also describes the characterization of binding by measuring the thermal melting temperature and surface plasmon resonance and by specific staining of telomeres (TTAGGG)n in human cells. Microheterogeneity was also investigated by high-resolution mass spectrometry. We found that the optimal compound as the hinge segment for telomere staining was [-NH(C2H4O)2(C 2H4)CO-] with tetramethylrhodamine as the fluorescent dye. © 2014 American Chemical Society.


Recently molecular targeting therapy has been applied to cancer chemotherapy, although in some cases side-effects are not negligible. Based on our bio-detection concept, that is, protein-protein interaction can be mimicked by using peptides, a novel cell-targeting concept designated peptide-vehicle has been proposed, which has conjugates consisting of the cancer cell recognition and cell penetrating peptides with anticancer drugs. The cancer cell surface protein can be captured by a cyclotide, containing protease resistant d-cystine. A library of cell penetrating peptides has been prepared and conjugated to the cyclotide. Anticancer molecules were recovered after clinical use, which were pooled, purified, and derivatized for loading into the vehicle. The present Letter describes construction of peptide-vehicles, bioconjugates focusing on more efficiency and cancer cell selective delivery for anticancer drugs. © 2014 Elsevier Ltd. All rights reserved.


Kasai K.,Japanese National Institute of Animal Health | Hirata A.,HiPep Laboratories | Ohyama T.,HiPep Laboratories | Nokihara K.,HiPep Laboratories | And 2 more authors.
FEBS Letters | Year: 2012

Characteristic differences of prions may account for the conformational diversity of the pathogenic isoform of prion protein (PrPSc). Here, we applied a protein detection procedure by using fluorescent-labelled peptides for detecting PrPSc. Five prion protein (PrP) related peptides were found to change significantly their fluorescent intensities with prion-affected animal samples. Their reactivity was different among atypical L-BSE, classical BSE and scrapie. The pull-down assay revealed that they precipitated PrP Sc specifically. These findings suggest that fluorescent intensity changes depend on peptide-PrPSc binding. This novel approach may distinguish the fine structural differences in PrPSc, which were not detected by the pull-down assay. Structured summary of protein interactions: PrP-peptides HPP01, 02, 03, 06, 11 physically interact with PrPSc of L-type atypical and classical BSEs, and scrapie by pull down. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Nokihara K.,HiPep Laboratories | Hirata A.,HiPep Laboratories | Sogon T.,HiPep Laboratories | Ohyama T.,HiPep Laboratories
Amino Acids | Year: 2012

Focusing on drug discovery non-proteinogenic amino acids have often been used as important building blocks for construction of compound libraries in the filed of combinatorial chemistry and chemical biology. Highly homogeneous l-mimosine, α-amino-β-(3-hydoxy-4-oxo-1,4-dihydropyridin-1-yl)- propanoic acid, a non-proteinogenic amino acid, has been successfully isolated and purified on an industrial scale from wild leaves of Leucaena (Leucaena leucocephala de Wit) which is a widely distributed legume in Okinawa, a sub-tropical island in Japan. Optical purity determinations used for quality control have been established through diastereomer formation. Physico-chemical properties and biological properties of purified mimosine have been clarified. Mimosine is sparingly soluble in water and organic solvents but can be dissolved in aqueous alkaline solution. The tyrosinase pathway is of particular interest in the cosmetic field, since mimosine is an analog of tyrosine. Thus the present purified mimosine have been tested in tyrosinase inhibitory assays. The IC 50 for tyrosinase inhibitory activity of purified Mim was compared with kojic acid. Mimosine shows significant inhibition of melanin production in murine melanoma cells. The derivatization of mimosine has been investigated with a focus on its use in conventional peptide syntheses to generate mimosyl peptides. N-(9-Fluorenylmethoxycarbonyloxy)-mimosine and resin-bound mimosine for solid-phase syntheses have also been performed. Highly homogeneous Mim is a useful material for the development of functional cosmetics or active pharmaceutical ingredients. © 2011 Springer-Verlag.


Nokihara K.,HiPep Laboratories | Yajima S.,Tokyo University of Agriculture | Hitara A.,HiPep Laboratories | Sogon T.,HiPep Laboratories | Yasuhara T.,Tokyo University of Agriculture
FEBS Letters | Year: 2013

Structural changes of proteins are thought to involve specific protein-peptide interactions, thus we hypothesize that certain peptides may contribute to the conformational change of prion proteins. Hence peptide libraries were constructed from partial digests of bovine brain. Using a recently developed conversion assay method, we have screened peptides responsible for structural conversion. Positive components were identified of which amino acid sequences were elucidated by top-down sequencing using mass spectrometry. A database search identified a peptide derived from synaptophysin. This peptide was chemically synthesized to confirm acceleration of the structural change of recombinant bovine prion protein. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Patent
Hipep Laboratories and Nippon Light Metal Co. | Date: 2011-04-06

A substrate for biochips which has a high probe loading amounts and a uniform immobilization density, and which further has a high detection sensitivity and a high reproducibility by preventing a non-specific adsorption of proteins, when used as a substrate for biochips for immobilizing probes composed of biologically relevant substances such as proteins and nucleic acids, is disclosed. Amino groups can be bound to the surface of the substrate uniformly, at a high density and stably by covalently immobilizing an amino group-containing polymer on the surface of the substrate. The probe immobilization rate is high and immobilizing density was uniform by immobilizing a probe composed of a biologically relevant substance such as a protein or nucleic acid by utilizing the amino groups. Further, detection sensitivity and reproducibility are high by inhibiting non-specific adsorption of proteins.


Patent
Hipep Laboratories and Nippon Light Metal Company | Date: 2010-03-31

Means for overcoming the problems which the conventional glass microchannel chips have are disclosed. That is, a microchannel chip in which microchannels can be formed at a low cost, and which has a high chemical resistance is disclosed. The microchannel chip is constituted by a substrate made of carbon, which has a channel in its surface; and a cover composed of a glass plate bonded to the substrate. The cover is bonded to the substrate by heating at least a part of the contact surface at which the substrate is in contact with the cover.


Patent
Nippon Light Metal Company and Hipep Laboratories | Date: 2014-07-22

A substrate for biochips which has a high probe loading amounts and a uniform immobilization density, and which further has a high detection sensitivity and a high reproducibility by preventing a non-specific adsorption of proteins, when used as a substrate for biochips for immobilizing probes composed of biologically relevant substances such as proteins and nucleic acids, is disclosed. Amino groups can be bound to the surface of the substrate uniformly, at a high density and stably by covalently immobilizing an amino group-containing polymer on the surface of the substrate. The probe immobilization rate is high and immobilizing density was uniform by immobilizing a probe composed of a biologically relevant substance such as a protein or nucleic acid by utilizing the amino groups. Further, detection sensitivity and reproducibility are high by inhibiting non-specific adsorption of proteins.


Patent
Hipep Laboratories | Date: 2012-01-18

Disclosed is an antioxidant which can exhibit a higher antioxidant ability than known antioxidative peptides. The antioxidant according to the present invention comprises mimosine and/or a mimosine-containing pcptide(s). The mimosine-containing peptide is a peptide which comprises at least one mimosine residue in its amino acid sequence. Mimosine has stronger antioxidant potency than known antioxidative tripeptides even when used as it is alone, and therefore is useful as an antioxidant. In addition, the antioxidant action of a peptide can be increased by introducing mimosine thereinto, thereby obtaining a peptide with higher antioxidant potency than the original one.

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