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1.
Akira Minami Yuuki Kurebayashi Tadanobu Takahashi Tadamune Otsubo Kiyoshi Ikeda Takashi Suzuki 《International journal of molecular sciences》2021,22(6)
Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme activity in mammalian tissues. Sialidase activity in the rat hippocampus detected with BTP3-Neu5Ac increases rapidly by neuronal depolarization. It is presumed that an increased sialidase activity in conjunction with neural excitation is involved in the formation of the neural circuit for memory. Since sialidase inhibits the exocytosis of the excitatory neurotransmitter glutamate, the increased sialidase activity by neural excitation might play a role in the negative feedback mechanism against the glutamate release. Mammalian tissues other than the brain have also been stained with BTP3-Neu5Ac. On the basis of information on the sialidase activity imaging in the pancreas, it was found that sialidase inhibitor can be used as an anti-diabetic drug that can avoid hypoglycemia, a serious side effect of insulin secretagogues. In this review, we discuss the role of sialidase in the brain as well as in the pancreas and skin, as revealed by using a sialidase activity imaging probe. We also present the detection of influenza virus with BTP3-Neu5Ac and modification of BTP3-Neu5Ac. 相似文献
2.
Takashi Ohnishi Yuki Ogawa Kota Suda Miki Komatsu Satoko Matsumoto Harmon Mitsuru Asukai Masahiko Takahata Norimasa Iwasaki Akio Minami 《International journal of molecular sciences》2021,22(9)
Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition. 相似文献
3.
4.
Shohei Minagawa Shoji Fujiwara Takeshi Hashimoto Takashi Hayashita 《International journal of molecular sciences》2021,22(9)
Cyclodextrins (CyDs) are water-soluble host molecules possessing a nanosized hydrophobic cavity. In the realm of molecular recognition, this cavity is used not only as a recognition site but also as a reaction medium, where a hydrophobic sensor recognizes a guest molecule. Based on the latter concept, we have designed a novel supramolecular sensing system composed of Zn(II)-dipicolylamine metal complex-based azobenzene (1-Zn) and 3A-amino-3A-deoxy-(2AS,3AS)-γ-cyclodextrin (3-NH2-γ-CyD) for sensing adenosine-5′-triphosphate (ATP). 1-Zn showed redshifts in the UV-Vis spectra and induced circular dichroism (ICD) only when both ATP and 3-NH2-γ-CyD were present. Calculations of equilibrium constants indicated that the amino group of 3-NH2-γ-CyD was involved in the formation of supramolecular 1-Zn/3-NH2-γ-CyD/ATP. The Job plot of the ICD spectral response revealed that the stoichiometry of 1-Zn/3-NH2-γ-CyD/ATP was 2:1:1. The pH effect was examined and 1-Zn/3-NH2-γ-CyD/ATP was most stable in the neutral condition. The NOESY spectrum suggested the localization of 1-Zn in the 3-NH2-γ-CyD cavity. Based on the obtained results, the metal coordination interaction of 1-Zn and the electrostatic interaction of 3-NH2-γ-CyD were found to take place for ATP recognition. The “reaction medium approach” enabled us to develop a supramolecular sensing system that undergoes multi-point interactions in water. This study is the first step in the design of a selective sensing system based on a good understanding of supramolecular structures. 相似文献
5.
Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile. 相似文献
6.
7.
Sugawara F. Aoki K. Yamaguchi H. Sasaki K. Sasaki T. Fujisaki H. 《Electron Device Letters, IEEE》1997,18(10):483-485
A new lateral MOS-gated thyristor, called the Base-Current-Controlled Thyristor, is described. This device is designed so that most holes at the on-stage reach the P base through the floating P+ region adjacent to the P base and the on-state MOSFET. At the turn-off stage, the interruption of the hole current to the P base due to switching off the above MOSFET occurs simultaneously with the conventional turn-off operation. The concept of this device is verified experimentally by using the fabricated lateral device with the external MOSFET. This device exhibits a better trade-off relation between the on-state voltage and the turn-off time compared uith the conventional MOS-gated thyristor 相似文献
8.
K Takeda K Saito K Makino Y Saito S Aoki T Koji K Matsumura Y Nomura T Kitano T Nakagawa 《Canadian Metallurgical Quarterly》1997,38(4):559-563
Due to the changes in the frequency of penicillin-resistant strains of S. pneumoniae, it is necessary to perform surveillance studies of bacterial resistance. Isolates from the upper respiratory tract of asymptomatic children have been useful. There is no information about the difference between isolates from children with and without upper respiratory tract infection (URTI). The objective of the authors in this paper is to establish the prevalence of carrier-state, serotype and antimicrobial resistance of S. pneumoniae isolates from children with and without acute upper respiratory tract infection (URTI) in a rural area in Mexico. A cross-sectional comparative study was performed in Tlaxcala, Mexico. Children from one month 5 years of age were included. Nasopharyngeal swabs were obtained. Identification was done by international microbiology standards. Serotyping was done by the capsular Quellung test. The susceptibility testing was performed by the agar dilution method. Four-hundred and fifty patients were included. S. pneumoniae was isolated in 134 children (29.7%). Frequency of carriers was greater in patients with URTI (107/323) than without URTI (27/127) (33.1% vs. 21.1% p = 0.012, OR 1.84, IC 95% 1.1-3.08). The six most frequent serotypes were: 6B (16.4%); 19F (11.9%); 19A (6.7%); 14, 23F, and 35 (5.2% each), with no difference among the groups. Only 3% of the strains had high level resistance to penicillin, and 12.6% had intermediate resistance, and for ampicillin 4%, amoxicillin 4%, amoxicillin-clavulanate 4%, ceftriaxone 3%, cefotaxime 1.5%, erythromycin 6%, miocamycin 3%, chloramphenicol 4%, and vancomycin 0%. Trimethoprim-sulfamethoxazole resistance was very high (42%). In conclusion, colonization is higher in children with URTI. Five of the most frequent serotypes identified in this study were the same as those identified in patients with S. pneumoniae invasive diseases in Mexico City. In Tlaxcala, Mexico, beta-lactams could be the drug of choice for the treatment of S. pneumoniae lower respiratory tract infections. It is necessary to perform clinical assays to evaluate the efficacy of trimethoprim-sulfamethoxazole due to the high resistance in vitro. 相似文献
9.
Masatsune Kato Takaaki Aoki Takashi Noji Yasuhiro Ono Yoji Koike Tomoyuki Hikita Yoshitami Saito 《Journal of Superconductivity and Novel Magnetism》1994,7(1):37-38
We have investigated the relation between the crystal structure and superconductivity in La1.9Bi0.1CuO4+δ , in which the phase separation observed in La2CuO4+δ is suppressed. A phase diagram in theT?δ plane is given for La1.9Bi0.1CuO4+δ with excess oxygen. For very smallδ values, the crystal structure is orthorhombic, and an orthorhombic-tetragonal phase transition occurs markedly atδ ~ 0.03 in the measured temperature range between 13 and 293 K. Superconductivity is observed in the range of 0.04<δ<0.11. This is clear evidence thathigh-T c superconductivity also appears in the tetragonal phase. 相似文献
10.
E Orgnero de Gaisán C Maldonado MF Diaz Gavier A Aoki 《Canadian Metallurgical Quarterly》1997,179(5):453-460
A bioassay system for rapid detection of carcinogenic agents has been developed using male Fischer 344 rats to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system, called the medium-term liver bioassay, is fundamentally based on the 2-stage hypothesis of tumor production, employing initiation by diethylnitrosamine (200 mg/kg, i.p.) in the first stage and test chemical administration during the second, in combination with two-thirds partial hepatectomy. It requires only 8 wk for animal experimentation and a further few weeks for quantitative analysis of immunohistochemically demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 291 chemicals/substances have already been analyzed in our laboratory. Among 63 chemicals that were proved to be carcinogenic in the liver of rat and/or mouse, 57 (90%) gave positive results irrespective of their mutagenicity. Negative compounds include peroxisome proliferators and tamoxifen. Even nonhepatocarcinogens were positive at a rate of 24%. Eighty-six percent (12/14) of mouse liver carcinogens were also positive. On the other hand, only 2 out of 45 noncarcinogens showed very weak positivity. Thus, the efficacy of the system for hepatocarcinogens has been well established. This bioassay is increasingly regarded as an appropriate alternative test for carcinogenicity risk assessment and is practically used for a rapid evaluation of hepatocarcinogenicity of chemicals. 相似文献