Keiko Ueno-Shuto  Shunsuke Kamei  Megumi Hayashi  Ayami Fukuyama  Yuji Uchida  Naofumi Tokutomi  Mary Ann Suico  Hirofumi Kai  Tsuyoshi Shuto 《International journal of molecular sciences》2022,23(14)

Cystic fibrosis (CF) is a hereditary disease typically characterized by infection-associated chronic lung inflammation. The persistent activation of toll-like receptor (TLR) signals is considered one of the mechanisms for the CF hyperinflammatory phenotype; however, how negative regulatory signals of TLRs associate with CF inflammation is still elusive. Here, we showed that the cell surface expression of a single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule (SIGIRR), a membrane protein essential for suppressing TLRs- and IL-1R-dependent signals, was remarkably decreased in CF airway epithelial cells compared to non-CF cells. Notably, CF airway epithelial cells specifically and highly expressed a unique, alternative splice isoform of the SIGIRR that lacks exon 8 (Δ8-SIGIRR), which results in the production of a C-terminal truncated form of the SIGIRR. Δ8-SIGIRR was expressed intracellularly, and its over-expression abolished the cell surface expression and function of the full-length SIGIRR (WT-SIGIRR), indicating its dominant-negative effect leading to the deficiency of anti-inflammatory activity in CF cells. Consistently, IL-37, a ligand for the SIGIRR, failed to suppress viral dsRNA analogue poly(I:C)-dependent JNK activation and IL-8 production, confirming the reduction in the functional WT-SIGIRR expression in the CF cells. Together, our studies reveal that SIGIRR-dependent anti-inflammatory activity is defective in CF airway epithelial cells due to the unique splicing switch of the SIGIRR gene and provides the first evidence of IL-37-SIGIRR signaling as a target of CF airway inflammation.  相似文献   

    

Katsuaki Ieguchi  Masabumi Funakoshi  Taishi Mishima  Kohtaro Takizawa  Tsutomu Omori  Fumio Nakamura  Makoto Watanabe  Mayumi Tsuji  Yuji Kiuchi  Shinichi Kobayashi  Takuya Tsunoda  Yoshiro Maru  Satoshi Wada 《International journal of molecular sciences》2022,23(18)

Emerging evidence suggests that neural activity contributes to tumor initiation and its acquisition of metastatic properties. More specifically, it has been reported that the sympathetic nervous system regulates tumor angiogenesis, tumor growth, and metastasis. The function of the sympathetic nervous system in primary tumors has been gradually elucidated. However, its functions in pre-metastatic environments and/or the preparation of metastatic environments far from the primary sites are still unknown. To investigate the role of the sympathetic nervous system in pre-metastatic environments, we performed chemical sympathectomy using 6-OHDA in mice and observed a decrease in lung metastasis by attenuating the recruitment of myeloid-derived suppressor cells. Furthermore, we note that neuro-immune cell interactions could be observed in tumor-bearing mouse lungs in conjunction with the decreased expression of Sema3A. These data indicate that the sympathetic nervous system contributes to the preparation of pre-metastatic microenvironments in the lungs, which are mediated by neuro-immune cell interactions.  相似文献   

    

Dr. Shinya Matsuda  Dr. Yuta Tsunematsu  Takuma Matsushita  Yuji Ogata  Shihomi Hachiya  Dr. Shinji Kishimoto  Dr. Noriyuki Miyoshi  Prof. Dr. Kenji Watanabe 《Chembiochem : a European journal of chemical biology》2022,23(4):e202100645

Biosynthetic genes are not only responsible for the formation of bioactive substances but also suited for other applications including gene therapy. To test the feasibility of human cells producing antibiotics in situ when provided with a heterologous biosynthetic gene, we focused on cytochrome P450, the class of enzymes important in conferring bioactivity to natural product precursors. We selected Fma-P450 that plays a central role in the fumagillin antimicrobial biosynthesis in Aspergillus fumigatus to examine fungal metabolite production by HeLa cells that express fma-P450 heterologously. Here we show that HeLa cells harboring fma-P450 can biosynthesize 5-hydroxyl-β-trans-bergamoten and cytotoxic 5-epi-demethoxyfumagillol when supplemented with the nontoxic precursor β-trans-bergamotene. While the production level was insufficient to effect cell death, we demonstrate that programming human cells to autogenerate antibiotics by introducing a heterologous biosynthetic gene is feasible.  相似文献   

    

Reiko Isa  Mano Horinaka  Taku Tsukamoto  Kentaro Mizuhara  Yuto Fujibayashi  Yoko Taminishi-Katsuragawa  Haruya Okamoto  Shusuke Yasuda  Yuka Kawaji-Kanayama  Yayoi Matsumura-Kimoto  Shinsuke Mizutani  Yuji Shimura  Masafumi Taniwaki  Toshiyuki Sakai  Junya Kuroda 《International journal of molecular sciences》2022,23(6)

Multiple myeloma (MM) is characterized by remarkable cytogenetic/molecular heterogeneity among patients and intraclonal diversity even in a single patient. We previously demonstrated that PDPK1, the master kinase of series of AGC kinases, is universally active in MM, and plays pivotal roles in cell proliferation and cell survival of myeloma cells regardless of the profiles of cytogenetic and genetic abnormalities. This study investigated the therapeutic efficacy and mechanism of action of dual blockade of two major PDPK1 substrates, RSK2 and AKT, in MM. The combinatory treatment of BI-D1870, an inhibitor for N-terminal kinase domain (NTKD) of RSK2, and ipatasertib, an inhibitor for AKT, showed the additive to synergistic anti-tumor effect on human MM-derived cell lines (HMCLs) with active RSK2-NTKD and AKT, by enhancing apoptotic induction with BIM and BID activation. Moreover, the dual blockade of RSK2 and AKT exerted robust molecular effects on critical gene sets associated with myeloma pathophysiologies, such as those with MYC, mTOR, STK33, ribosomal biogenesis, or cell-extrinsic stimuli of soluble factors, in HMCLs. These results provide the biological and molecular rationales for the dual-targeting strategy for RSK2 and AKT, which may overcome the therapeutic difficulty due to cytogenetic/molecular heterogeneity in MM.  相似文献   

    

Salma O. M. Osman  Abu Sefyan I. Saad  Shota Tadano  Yoshiki Takeda  Takafumi Konaka  Yuji Yamasaki  Izzat S. A. Tahir  Hisashi Tsujimoto  Kinya Akashi 《International journal of molecular sciences》2022,23(5)

Wheat (Triticum aestivum L.) is known to be negatively affected by heat stress, and its production is threatened by global warming, particularly in arid regions. Thus, efforts to better understand the molecular responses of wheat to heat stress are required. In the present study, Fourier transform infrared (FTIR) spectroscopy, coupled with chemometrics, was applied to develop a protocol that monitors chemical changes in common wheat under heat stress. Wheat plants at the three-leaf stage were subjected to heat stress at a 42 °C daily maximum temperature for 3 days, and this led to delayed growth in comparison to that of the control. Measurement of FTIR spectra and their principal component analysis showed partially overlapping features between heat-stressed and control leaves. In contrast, supervised machine learning through linear discriminant analysis (LDA) of the spectra demonstrated clear discrimination of heat-stressed leaves from the controls. Analysis of LDA loading suggested that several wavenumbers in the fingerprinting region (400–1800 cm⁻¹) contributed significantly to their discrimination. Novel spectrum-based biomarkers were developed using these discriminative wavenumbers that enabled the successful diagnosis of heat-stressed leaves. Overall, these observations demonstrate the versatility of FTIR-based chemical fingerprints for use in heat-stress profiling in wheat.  相似文献   

    

Momoko Kasamatsu  Takeshi Arima  Toyo Ikebukuro  Yuji Nakano  Yutaro Tobita  Masaaki Uchiyama  Akira Shimizu  Hiroshi Takahashi 《International journal of molecular sciences》2022,23(17)

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Pawe&#x; Krukowski  Takuma Hattori  Megumi Akai-Kasaya  Akira Saito  Hideji Osuga  Yuji Kuwahara 《International journal of molecular sciences》2022,23(23)

Light emission from the M-type enantiomer of a helicene derivative (2,13-bis(hydroxymethyl)[7]-thiaheterohelicene) adsorbed on the clean Au(111) and the C₆₀-covered Au(111) surfaces were investigated by tunneling-current-induced light-emission technique. Plasmon-originated light emission was observed on the helicence/Au(111) surface and it was strongly suppressed on the area where the helicene molecules were adsorbed at the edges of the Au(111) terraces. To avoid luminescence quenching of excited helicene molecules and to suppress strong plasmon light emission from the Au(111) surface, C₆₀ layers were used as decoupling buffer layers between helicene molecules and the Au(111) surface. Helicene molecules were adsorbed preferentially on the Au(111) surface rather than on the C₆₀ buffer layers due to the small interaction of the molecules and C₆₀ islands. This fact motivated us to deposit a multilayer of helicene molecules onto the C₆₀ layers grown on the Au(111) surface, leading to the fact that the helicene/C₆₀ multilayer showed strong luminescence with the molecules character. We consider that such strong light emission from the multilayer of helicene molecules has a plasmon origin strongly modulated by the molecular electronic states of (M)-[7]TH-diol molecules.  相似文献   

    

Daisuke Shimamoto  Yuichi Tominaga  Yuji Hotta 《Advanced Composite Materials》2016,25(6):71-79

The effects of microwave irradiation for resin-curing of carbon fiber/epoxy resin composite (CFRTS), which was fabricated by vacuum-assisted resin transfer molding (VARTM) method, were investigated at 2.45 GHz frequency. The mechanical properties of CFRTS cured by microwave irradiation for 20 min at 120 °C were similar as compared to the conventional oven for 300 min at 120 °C. Moreover, the CFRTS irradiated by microwave had better adherence property between fiber and resin as compared to conventional oven at same resin-curing time. From the relation between resin-curing and mechanical property, it was found that the curing rate of microwave-irradiated CFRTS was 15 times faster as compared to conventional heating. Furthermore, the activation energies for resin-curing reaction on conventional- and microwave-cured CFRTS were estimated to be 2.7 and 1.3 × 10⁴ J/mol, respectively. The resin-curing reaction in CFRTS prepared by VARTM method was significantly promoted by microwave irradiation at short time.  相似文献   

Novel double staining of the stratum corneum with fluorescent ε-poly-l-lysine and anionic dextran     

Moemi Yoshida  Sana Numajiri  Nao Notani  Koji Nomoto  Hiroya Urabe  Jun-ichi Sato  Yuji Yamashita  Tetsuji Hirao 《International journal of cosmetic science》2023,45(3):400-412

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Suga  Satoshi  Fujimori  Ryu  Yamada  Yuji  Ihara  Fumito  Takamura  Daiki  Hayashi  Ken  Kurihara  Satoshi 《Artificial Life and Robotics》2023,28(2):367-380

Traffic congestion has become one of the most pressing social problems in today’s society, and research into appropriate traffic signal control is actively underway. At present, most traffic signal control methods define traffic signal parameters on the basis of traffic information such as the number of passing vehicles. Installing sensors at a vast number of intersections is necessary for more precise and real-time adaptive control, but this is unrealistic from the viewpoint of cost. As an alternative, we propose a swarm intelligence-based methodology that creates routes with a similar traffic volume using the traffic information from intersections already equipped with sensors and interpolates this information in the intersections without sensors in real time. Our simulation results show that the proposed methodology can effectively create similar traffic routes for main traffic flows with high traffic volumes. The results also show that it has an excellent interpolation performance for heavy traffic flows and can adapt and interpolate to situations where traffic flow changes suddenly. Moreover, the interpolation results are highly accurate at a road link where traffic flows confluence. We also developed an interpolation algorithm that is adaptable to traffic patterns with confluence traffic flows. Experiments were conducted with a simulation of merging traffic flows and the proposed method showed good results.

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