著者

Takekatsu Shibata Ryuta Urakawa Chikako Ono Yukihiro Akeda Takayoshi Sakai Shigeto Hamaguchi Kiyoto Takamori Tsuyoshi Inoue Kazunori Tomono Kiyoshi Konishi Yoshiharu Matsuura

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.4, no.3, pp.78-84, 2021 (Released:2021-05-26)

参考文献数

39

被引用文献数

8

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Matching transformation system (MA-T) is an on-demand aqueous chlorine dioxide solution. It is a disinfectant developed to maximize the safety of chlorine dioxide radical in water and its effectiveness against various microorganisms. In this study, we examined the safety and effectiveness of MA-T for its use in various infectious disease countermeasures, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consider if MA-T can be implemented in society. To validate the safety of MA-T, we conducted safety tests and efficacy tests in accordance with GLP-based reliability criteria. To evaluate the efficacy, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) confirmation tests against various bacteria, and virus inactivation test against various viruses including SARS-CoV-2 by TCID50 method were performed. The results of safety tests showed that MA-T was at least as safe as Japanese tap water. As a result of efficacy tests for microorganisms, MA-T was effective against many bacteria. Efficacy tests for virus showed that MA-T inactivates SARS-CoV-1, Middle East respiratory syndrome coronavirus (MERS-CoV), rotavirus A (RV-A), hepatitis C virus (HCV), dengue virus (DENV), and hepatitis B virus (HBV). MA-T also inactivated 99.98% of SARS-CoV-2, which is equivalent to ethanol for disinfection. MA-T has proven to be a safe and effective disinfectant. MA-T is a next-generation disinfectant that has the potential to be safer and more effective than conventional chlorine disinfectants and other disinfectants. It also proved to be an effective disinfectant against SARS-CoV-2, which is currently causing pandemic all over the world.

著者

Megumi Yahara Kazuyuki Niki Keita Ueno Mio Okamoto Takeshi Okuda Hiroyuki Tanaka Yasuo Naito Ryouhei Ishii Mikiko Ueda Toshinori Ito

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.7, pp.1019-1023, 2021-07-01 (Released:2021-07-01)

参考文献数

20

被引用文献数

22

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To prevent cognitive decline, non-pharmacological therapies such as reminiscence for mild cognitive impairment (MCI) are required, however, the use of nursing homes was limited due to coronavirus disease 2019 (COVID-19). Therefore, the demand for remote-care is increasing. We hypothesized that immersive virtual reality (iVR) could be used more effectively than conventional reminiscence for anxiety. We first examined the effectiveness and safety of reminiscence using iVR (iVR reminiscence session) in patients with MCI. After COVID-19 imposed restriction on visiting nursing homes, we conducted online iVR reminiscence session (remote iVR reminiscence session) and compared its effectiveness with that of interpersonal iVR reminiscence session (face-to-face iVR reminiscence session). The results of two elderly with MCI suggested that iVR reminiscence could reduce anxiety and the burden of care without serious side effects. The effects of remote iVR reminiscence might be almost as effective as those of face-to-face one.

著者

Satoshi Nakao Haruna Hatahira Sayaka Sasaoka Shiori Hasegawa Yumi Motooka Natsumi Ueda Junko Abe Akiho Fukuda Misa Naganuma Hiroyuki Kanoh Mariko Seishima Motoyuki Ishiguro Yasutomi Kinosada Mitsuhiro Nakamura

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.12, pp.2158-2165, 2017-12-01 (Released:2017-12-01)

参考文献数

50

被引用文献数

10 27

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Drug-induced photosensitivity (DIP) refers to the development of cutaneous disorders caused by the combined effects of different medications and light. The aim of this study was to obtain new information on drug risk comparisons and on DIP onset profiles, including seasonal variations, for clinically used prescription drugs. We analyzed reports of DIP recorded in the Japanese Adverse Drug Event Report (JADER) database using a reporting odds ratio (ROR). We also used Weibull proportional-hazards models for each drug to examine the patterns of DIP. The JADER database contains 430587 reports recorded from April 2004 to November 2016. The ROR values (95% confidence interval [CI]) of losartan/hydrochlorothiazide (HCTZ), valsartan/HCTZ, and ketoprofen were 214.5 (162.1–283.9), 104.7 (66.3–165.5), and 117.9 (76.6–181.5), respectively. For time-to-onset analysis, the median durations (interquartile range) for DIP caused by losartan/HCTZ, valsartan/HCTZ, and ketoprofen were 56 (41–78), 49 (38–88), and 8 (2–14) days, respectively. The lower limit of the 95% CI for the Weibull shape parameter β value for losartan/HCTZ was greater than 1. More than half of the reports of DIP onset following the administration of ketoprofen were recorded within 10 d of treatment initiation. The seasonal variation of photosensitivity reactions was shown to follow an annual sinusoidal pattern with a peak in April and May. Based on the results, losartan/HCTZ, valsartan/HCTZ, and ketoprofen should be used carefully in clinical practice to avoid DIP.

著者

Shouma Ishikawa Atsushi Sawamoto Satoshi Okuyama Mitsunari Nakajima

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.4, pp.550-556, 2021-04-01 (Released:2021-04-01)

参考文献数

23

被引用文献数

3

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We previously reported a screening method for caloric restriction mimetics (CRM), a group of plant-derived compounds capable of inducing good health and longevity. In the present study, we explored the possibility of using this method to screen CRM drugs for drug repositioning. The method, T-cell activation-inhibitory assay, is based on inductive logic. Most of CRM such as resveratrol have been reported to suppress T-cell activation and have anti-inflammatory functions. Here, we assessed the activity of 12 antiallergic drugs through T-cell activation-inhibitory assay and selected four that showed the lowest IC50 values—ibudilast (IC50 0.97 µM), azelastine (IC50 7.2 µM), epinastine (IC50 16 µM), and amlexanox (IC50 33 µM)—for further investigation. Because azelastine showed high cytotoxicity, we selected only the remaining three drugs to study their biological functions. We found that all the three drugs suppressed the expression of interleukin (IL)-6, an inflammatory cytokine, in lipopolysaccharide-treated macrophage cells, with ibudilast being the strongest suppressor. Ibudilast also suppressed the secretion of another inflammatory cytokine, tumor necrosis factor (TNF)-α, and the expression of an inflammatory enzyme, cyclooxygenase-2, in the cells. These results suggest that T-cell activation-inhibitory assay can be used to screen potential CRM drugs having anti-inflammatory functions for the purpose of drug repositioning.

著者

Haruyo Iwasawa Erika Morita Satoru Yui Masatoshi Yamazaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.1, pp.128-134, 2011-01-01 (Released:2011-01-01)

参考文献数

41

被引用文献数

30 52 14

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We previously reported that kiwi fruit is rich in polyphenols and has immunostimulatory activity. Polyphenols are widely known for having anti-oxidant effects. We also revealed potential anti-oxidant effects of kiwi fruit in vivo by oral administration to mice. Here, we compared the anti-oxidant effects of kiwi fruit with those of other fruits in vitro. Then, we examined the inhibitory effects of kiwi fruit on oxidation in the human body. There are two varieties of kiwi fruit, green kiwi and gold kiwi. We also examined variation between these varieties. Comparison of the anti-oxidant effects in vitro demonstrated that kiwi fruit had stronger anti-oxidant effects than orange and grapefruit, which are rich in vitamin C; gold kiwi had the strongest anti-oxidant effects. Kiwi fruit inhibited oxidation of biological substances in the human body. In particular, kiwi fruit may inhibit early lipid oxidation. In this study, kiwi fruit had strong anti-oxidant effects and may prevent the development and deterioration of diseases caused by oxidative stress.

著者

Aya Ueda Shinji Toki Chisato Kitayama Manabu Akazawa

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.7, pp.1135-1140, 2020-07-01 (Released:2020-07-01)

参考文献数

19

被引用文献数

4

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Inappropriately reduced doses (IRDs) of direct oral anticoagulants (DOACs) are common in clinical practice. We performed a retrospective review using electronic medical records of St. Marianna University School of Medicine Hospital (a 1200-bed teaching hospital in Japan) to address the prevalence of IRDs and patient-related factors that result in IRDs. We also surveyed DOAC-treated patients who were hospitalized due to a stroke during the 5-year study period to analyze the association between stroke events and IRDs. We found that one in five patients who were newly prescribed a DOAC was treated with IRDs. Patients treated with edoxaban received the most IRDs (64%, 7/11), followed by those treated with dabigatran (50%, 1/2), apixaban (32%, 19/61), and rivaroxaban (27%, 12/44). Our analysis showed that the renal function (measured as serum creatinine and creatinine clearance values) and age are possible factors influencing dose reduction. The HAS-BLED score and antiplatelet use were not associated with IRD prescription. An analysis of the 5-year hospital records revealed 20 stroke cases despite ongoing treatments with DOACs, and IRDs were noted in three of these cases. In all three cases, the patients had been on an IRD of rivaroxaban. To prevent IRDs of DOACs, we suggest that a clinical protocol be incorporated into formularies to support the prescription process.

著者

三宅 昭夫 岡 良和 万木 庄次郎

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.23, no.7, pp.1500-1504, 1975-07-25 (Released:2008-03-31)

被引用文献数

1 6

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Photochemical reactions of tetraazanaphthalene derivatives, I, II, and III, with alcohols and cyclic ethers in the presence of photosensitizer resulted in selective addition at the 3, 4 C=N bond to give substituted-3, 4-dihydro derivatives. Potential diuretic activity was shown by many of the obtained compounds.

著者

Shungo Imai Yoh Takekuma Takayuki Miyai Mitsuru Sugawara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.1, pp.188-193, 2020-01-01 (Released:2020-01-01)

参考文献数

18

被引用文献数

22

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This study aimed to construct an optimal algorithm for initial dose settings of vancomycin (VCM) using machine learning (ML) with decision tree (DT) analysis. Patients who were administered intravenous VCM and underwent therapeutic drug monitoring (TDM) at the Hokkaido University Hospital were enrolled. The study period was November 2011 to March 2019. In total, 654 patients were included in the study. Patients were divided into two groups, training (patients who received VCM from November 2011 to December 2017; n = 496) and testing (patients who received VCM from January 2018 to March 2019; n = 158) groups. For the training group, DT analysis of the classification and regression tree algorithm was performed to construct an algorithm (called DT algorithm) for the initial dose settings of VCM. For the testing group, the rates of attaining the VCM therapeutic range (trough value = 10–15 and 10–20 mg/L) with the DT algorithm and three conventional dose-setting methods were compared for model evaluation. The DT algorithm was constructed to be used for patients with estimated glomerular filtration rate ≥50 mL/min and body weight ≥40 kg. As a result, the recommended daily doses ranged from 20.0 to 58.1 mg/kg. In model evaluation, the DT algorithm obtained the highest rates of attaining the VCM therapeutic range compared to conventional dose-setting methods. Therefore, our DT algorithm can be applied to clinical practice. In addition, ML is useful for setting drug doses.

著者

Hirotomo Moriwaki Yu-Shi Tian Norihito Kawashita Tatsuya Takagi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.67, no.5, pp.426-432, 2019-05-01 (Released:2019-05-01)

参考文献数

22

被引用文献数

3

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Quantitative structure–activity relationship (QSAR) techniques, especially those that possess three-dimensional attributes, such as the comparative molecular field analysis (CoMFA), are frequently used in modern-day drug design and other related research domains. However, the requirement for accurate alignment of compounds in CoMFA increases the difficulties encountered in its use. This has led to the development of several techniques—such as VolSurf, Grid-independent descriptors (GRIND), and Anchor-GRIND—which do not require such an alignment. We propose a technique to construct the prediction model that uses molecular interaction field grid potentials as inputs to convolutional neural network. The proposed model has been found to demonstrate higher accuracy compared to the conventional descriptor-based QSAR models as well as Anchor-GRIND techniques. In addition, the method is target independent, and is capable of providing useful information regarding the importance of individual atoms constituting the compounds contained in the chemical dataset used in the proposed analysis. In view of these advantages, the proposed technique is expected to find wide applications in future drug-design operations.

著者

Yu Fukuoka El-Sayed Khafagy Takahiro Goto Noriyasu Kamei Kozo Takayama Nicholas A. Peppas Mariko Takeda-Morishita

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.5, pp.811-814, 2018-05-01 (Released:2018-05-01)

参考文献数

14

被引用文献数

24

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In previous studies we showed that the complexation hydrogels based in poly(methacrylic acid-g-ethylene glycol) [P(MAA-g-EG)] rapidly release insulin in the intestine owing to their pH-dependent complexation properties; they also exhibit a high insulin-loading efficiency, enzyme-inhibiting properties, and mucoadhesive characteristics. Cell-penetrating peptides (CPPs), such as oligoarginines [hexa-arginine (R6), comprising six arginine residues], have been employed as useful tools for the oral delivery of therapeutic macromolecules. The aim of our study was to investigate the combination strategy of using P(MAA-g-EG) hydrogels with R6-based CPPs to improve the intestinal absorption of insulin. A high efficiency of loading into crosslinked P(MAA-g-EG) hydrogels was observed for insulin (96.1±1.4%) and R6 (46.6±3.8%). In addition, immediate release of the loaded insulin and R6 from these hydrogels was observed at pH 7.4 (80% was released in approximately 30 min). Consequently, a strong hypoglycemic response was observed (approximately 18% reduction in blood glucose levels) accompanied by an improvement in insulin absorption after the co-administration of insulin-loaded particles (ILP) and R6-loaded particles (ALP) into closed rat ileal segments compared with that after ILP administration alone. These results indicate that the combination of P(MAA-g-EG) hydrogels with CPPs may be a promising strategy for the oral delivery of various insulin preparations as an alternative to conventional parenteral routes.

著者

Jun Shimokawa

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.2, pp.105-115, 2018-02-01 (Released:2018-02-01)

参考文献数

153

被引用文献数

4

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The divergent total syntheses of three types of heteropolycyclic natural products, namely gelsedine-type alkaloids, amathaspiramide alkaloids, and erythrina alkaloids, are outlined. A strategy involving a late-stage pluripotent common synthetic intermediate prepared via original and innovative transformations was employed. A brief description of the philosophy and criteria for choosing the synthetic targets and common synthetic precursors, as well as details regarding the development of the overall synthetic schemes from a common intermediate are discussed.

著者

Adriana Meri Mestrimer Felipe Vinicius Pires Rincão Fabrício José Benati Rosa Elisa Carvalho Linhares Karen Janaina Galina Cleyton Eduardo Mendes de Toledo Gisely Cristiny Lopes João Carlos Palazzo de Mello Carlos Nozawa

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.29, no.6, pp.1092-1095, 2006 (Released:2006-06-01)

参考文献数

22

被引用文献数

22 60

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Crude extract (CE) and aqueous (AqF) and ethyl acetate (EtOAcF) fractions of Guazuma ulmifolia LAM., Sterculiaceae and the corresponding AqF, EtOAcF of Stryphnodendron adstringens (MART.) COVILLE, Leguminosae were tested for their antiviral activity against poliovirus 1 (P-1) and bovine herpesvirus 1 (BHV-1) in HEp-2 cultured cells. The antiviral activity was monitored by plaque assay and immunofluorescence assay (IFA) under virucidal and therapeutic protocols. The therapeutic protocol demonstrated statistically significant positive results with both plants and for both virus strains. The highest percentages of viral inhibition were found for G. ulmifolia EtOAcF which inhibited BHV-1 and P-1 replication by 100% and 99%, respectively (p<0.05, Student's t-test). For S. adstringens, AqF was the most efficient, inhibiting BHV-1 and P-1 by 97% and 93%, respectively (p<0.05). In the virucidal protocol, G. ulmifolia CE inhibited the replication of BHV-1 and P-1 by 60% and 26%, respectively (p<0.05), while, for S. adstringens, inhibition of 62% (p<0.05) was demonstrated only with EtOAcF for P-1. IFA demonstrated that the greatest reduction in fluorescent cell number occurred with G. ulmifolia, under the therapeutic protocol for both virus strains. However, AqF and EtOAcF of S. adstringens were most efficient with the virucidal protocol for P-1. In conclusion, we demonstrated that G. ulmifolia and S. adstringens inhibited BHV-1 and P-1 replication, as well as, blocked the synthesis of viral antigens in infected cell cultures.

著者

Masashi Kitamura Masako Aragane Kou Nakamura Tatsushi Adachi Kazuhito Watanabe Yohei Sasaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.8, pp.1303-1306, 2018-08-01 (Released:2018-08-01)

参考文献数

15

被引用文献数

9

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Cannabis sativa L. is cultivated worldwide for a variety of purposes, but its cultivation and possession are regulated by law in many countries, necessitating accurate detection methods. We previously reported a DNA-based C. sativa identification method using the loop-mediated isothermal amplification (LAMP) assay. Although the LAMP technique can be used for on-site detection, our previous protocol took about 90 min from sampling to detection. In this study, we report an on-site protocol that can be completed in 30 min for C. sativa identification based on a modified LAMP system. Under optimal conditions, the LAMP reaction started at approximately 10 min and was completed within 20 min at 63°C. It had high sensitivity (10 pg of purified DNA). Its specificity for C. sativa was confirmed by examining 20 strains of C. sativa and 50 other species samples. With a simple DNA extraction method, the entire procedure from DNA extraction to detection required only 30 min. Using the protocol, we were able to identify C. sativa from various plant parts, such as the leaf, stem, root, seed, and resin derived from C. sativa extracts. As the entire procedure was completed using a single portable device and the results could be evaluated by visual detection, the protocol could be used for on-site detection and is expected to contribute to the regulation of C. sativa.

著者

Tomoichiro Asano Midori Fujishiro Akifumi Kushiyama Yusuke Nakatsu Masayasu Yoneda Hideaki Kamata Hideyuki Sakoda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.9, pp.1610-1616, 2007-09-01 (Released:2007-09-01)

参考文献数

44

被引用文献数

29 56

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Inositol phospholipids phosphorylated on D3-position of their inositol rings (3-phosphoinositides) are known to play important roles in various cellular events. Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110α or p110β. Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis. Accumulated PI(3,4,5)P3 activates several serine/threonine kinases containing a PH (pleckstrin homology) domain, including Akt, atypical PKCs, p70S6 kinase and GSK.In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations. Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus.

著者

Yo Muraki Midori Yamasaki Hirohisa Takeuchi Kimio Tohyama Noriyasu Sano Takanori Matsuo

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c17-00811, (Released:2018-01-06)

参考文献数

36

被引用文献数

6

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Pulmonary hypertension (PH) is a life-threatening lung disease. Despite the availability of several approved drugs, the development of a new treatment method is needed because of poor prognosis. Tissue selective drug delivery systems can avoid the adverse effects of current therapy and enhance efficacy. We evaluated the possibility of delivering drugs to the lungs of a PH rat model using fluorescence dye-labeled nanosized liposomes. To evaluate the tissue distribution following systemic exposure, fluorescent dye-labeled, 40-180 nm liposomes with and without polyethylene glycol (PEG) were intravenously administered to a monocrotaline-induced PH (MCT) rat model and tissue fluorescence was measured. Fluorescent dye-containing liposomes were intratracheally administered to the MCT model to evaluate the distribution of the liposome-encapsulated compound following local administration to reduce systemic exposure. The lung vascular permeability, plasma concentration of surfactant protein (SP)-D, lung reactive oxygen species (ROS) production, and macrophage marker gene cluster of differentiation (CD68) expression were measured. PEG and 80-nm liposome accumulation in the lung was elevated in the MCT model compared to that in normal rats. The intratracheally administered liposomes were delivered selectively to the lungs of the MCT model. The lung vascular permeability, plasma SP-D concentration, and CD68 expression were significantly elevated in the lungs of the MCT model, and were all significantly and positively correlated to liposome lung accumulation. Liposomes can accumulate in the lungs of an MCT model by enhancing vascular permeability by the inflammatory response. Therefore, drug encapsulation in liposomes could be an effective method of drug delivery in patients with PH.

著者

Rina Abe Yuka Yagi Hidenori Tani

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.6, no.6, pp.226-228, 2023 (Released:2023-12-26)

参考文献数

21

被引用文献数

1

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Long non-coding RNAs (lncRNAs) are transcripts exceeding 200 nucleotides in length that do not code for proteins. However, they play pivotal roles in various biological processes. The mechanisms by which bacterial infections induce lncRNA expression remain elusive. Our past study, we identified a unique class of lncRNAs with short half-lives, less than 4 h in human HeLa cells. These short-lived lncRNAs include to many regulatory functions, such as HOTAIR, NEAT1, or GAS5. Due to their potential influence on human biology, these short-lived lncRNAs might serve as important markers to gauge the stress from bacterial infections. In this study, we identified three lncRNAs, named MIR22HG, GABPB1-AS1, and IDI2-AS1. Their expression significantly decreased after exposure to lipopolysaccharide, simulating bacterial infection in human A549 cells. Our findings suggest that short-lived lncRNAs react to bacterial infections, with their expression levels dropping notably. We propose that these lncRNAs could act as potential indicators of cellular responses to bacteria.

著者

Jun Ye Yuping Li Takeki Hamasaki Noboru Nakamichi Takaaki Komatsu Taichi Kashiwagi Kiichiro Teruya Ryuhei Nishikawa Takeshi Kawahara Kazuhiro Osada Kazuko Toh Masumi Abe Huaize Tian Shigeru Kabayama Kazumichi Otsubo Shinkatsu Morisawa Yoshinori Katakura Sanetaka Shirahata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.1, pp.19-26, 2008-01-01 (Released:2008-01-01)

参考文献数

86

被引用文献数

57 62

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Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Tumor cells are exposed to higher oxidative stress compared to normal cells. Numerous reports have demonstrated that the intracellular redox (oxidation/reduction) state is closely associated with the pattern of VEGF expression. Electrolyzed reduced water (ERW) produced near the cathode during the electrolysis of water scavenged intracellular H2O2 and decreased the release of H2O2 from a human lung adenocarcinoma cell line, A549, and down-regulated both VEGF transcription and protein secretion in a time-dependent manner. To investigate the signal transduction pathway involved in regulating VEGF expression, mitogen-activated kinase (MAPK) specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (ERK1/2 inhibitor) and JNKi (c-Jun N-terminal protein kinase inhibitor) were applied. The results showed that only PD98059 blocks VEGF expression, suggesting an important role for ERK1/2 in regulating VEGF expression in A549 cells. As well, ERW inhibited the activation of extracellular signal-regulated kinase (ERK) in a time-dependent manner. Co-culture experiments to analyze in vitro tubule formation assay revealed that A549 cell-derived conditioned medium significantly stimulated the formation of vascular tubules in all analyzed parameters; tubule total area, tubule junction, number of tubules, and total tubule length. ERW counteracted the effect of A549 cell-conditioned medium and decreased total tube length (p<0.01). The present study demonstrated that ERW down-regulated VEGF gene transcription and protein secretion through inactivation of ERK.

著者

Yurika Tahara Mikako Fujita Tianli Zhang Dongxing Wang Hiroshi Tateishi Akihiro Togami Perpetual Nyame Hiromi Terasawa Nami Monde Joyce Appiah-Kubi Wright Ofotsu Amesimeku Doaa Husham Majeed Alsaadi Mikiyo Wada Koji Sugimura Sevgi Gezici Halilibrahim Ciftci Faruk Karahan Nazim Sekeroglu Masami Otsuka Tomohiro Sawa Yosuke Maeda Takashi Watanabe Kazuaki Monde

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.11, pp.1535-1547, 2023-11-01 (Released:2023-11-01)

参考文献数

67

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The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.

著者

Miya Urui Yasuyuki Yamada Akira Nakagawa Fumihiko Sato Hiromichi Minami Nobukazu Shitan

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1494-1497, 2023-10-01 (Released:2023-10-01)

参考文献数

15

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Advancements in synthetic biology have facilitated the microbial production of valuable plant metabolites. However, constructing complete biosynthetic pathways within a single host organism remains challenging. To solve this problem, modular co-culture systems involving host organisms with partial pathways have been developed. We focused on Escherichia coli, a general host for metabolite production, and Pichia pastoris (Komagataella phaffii), a novel synthetic biology host due to its high expression of biosynthetic enzymes. Previously, we reported the co-culture of E. coli cells, which produce reticuline (an important intermediate for various alkaloids) from glycerol, with P. pastoris cells, which produce the valuable alkaloid stylopine from reticuline. However, Pichia cells inhibited E. coli growth and reticuline production. Therefore, we aimed to improve this co-culture system. We investigated the pre-culture time before co-culture to enhance E. coli growth and reticuline production. Additionally, we examined the optimal concentration of Pichia cells inoculated for co-culture and methanol addition during co-culture for the continuous expression of biosynthetic enzymes in Pichia cells. We successfully established an improved co-culture system that exhibited an 80-fold increase in productivity compared to previous methods. This enhanced system holds great potential for the rapid and large-scale production of various valuable plant metabolites.

著者

Fukie Niijima-Yaoita Masahiro Tsuchiya Hiroshi Ohtsu Kazuhiko Yanai Shunji Sugawara Yasuo Endo Takeshi Tadano

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.35, no.1, pp.91-97, 2012-01-01 (Released:2012-01-05)

参考文献数

35

被引用文献数

29 30

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Exercise necessitates a large supply of O2 and nutrients and rapid removal of CO2 and waste products. Histamine is a regulator of the microcirculation (which performs these exchanges), suggesting a possible involvement of histamine in exercise. Histamine is released from either mast cells or non-mast cells. In the latter, histamine is newly formed via the induction of histidine decarboxylase (HDC) in response to an appropriate stimulus, and it is released without being stored. Here, in mice, we examined the role of histamine or HDC induction in exercise. Prolonged walking (PW) (in a cylindrical cage turned electrically) increased HDC mRNA and HDC activity in quadriceps femoris muscles. Mice given a histamine H1-receptor antagonist [fexofenadine (peripherally acting) or pyrilamine (peripherally and centrally acting)] or an irreversible HDC inhibitor (α-fluoromethylhistidine) displayed less PW endurance than control mice. Ranitidine (H2-receptor antagonist) tended to reduce endurance. Other histamine-receptor (H3 and H4) antagonists had no significant effects on endurance. Mice deficient in HDC or histamine H1-receptors displayed markedly less endurance than control mice, and HDC activity in the quadriceps femoris of H1-deficient mice was rapidly elevated by PW. Fexofenadine significantly reduced the muscle levels of nitric oxide (NO) metabolites and glycogen after PW. The results support the ideas that (i) histamine is involved in protecting against exercise-induced fatigue or exhaustion, (ii) histamine exerts its protective effect via H1 receptors and the ensuing production of NO in skeletal muscle, and (iii) histamine is provided, at least in part, by HDC induction in skeletal muscles during prolonged exercise.