Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
最新号
選択された号の論文の11件中1~11を表示しています
Review
  • Atsushi Miyashita, Kazuhisa Sekimizu
    原稿種別: review-article
    2021 年 15 巻 2 号 p. 51-54
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/03/19
    ジャーナル フリー

    Bombyx mori, the silkworm, has biological functions in common with mammals, including humans. Since the molecular design of silkworm's innate immune system is analogous to that of mammals, understanding the silkworm's innate immunity is expected to contribute to the control of infection in humans. It is also possible to use silkworms to explore foodstuffs that activate innate immunity. Lactic acid bacteria have long been used in the production of fermented foods, and in recent years, their use as supplements has been attracting attention. Using silkworms, which are laboratory animals, functional lactic acid bacteria can be explored and isolated at low cost. Fermented foods produced by this method are expected to contribute to the maintenance of human health. In addition to the immune system, humans and silkworms share a common mechanism for maintaining blood glucose homeostasis, and it is possible to construct a pathological model of diabetes and search for therapeutic substances using silkworms. Taken together, we propose that the silkworm is useful for assessing the functions of lactic acid bacterial for health purposes.

Original Article
  • Shun Utsunomiya, Yusuke Kishi, Masafumi Tsuboi, Daichi Kawaguchi, Yuki ...
    原稿種別: research-article
    2021 年 15 巻 2 号 p. 55-65
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/03/08
    ジャーナル フリー

    Immature neurons undergo morphological and physiological maturation in order to establish neuronal networks. During neuronal maturation, a large number of genes change their transcriptional levels, and these changes may be mediated by chromatin modifiers. In this study, we found that the level of Ezh1, a component of Polycomb repressive complex 2 (PRC2), increases during neuronal maturation in mouse neocortical culture. In addition, conditional knockout of Ezh1 in post-mitotic excitatory neurons leads to downregulation of a set of genes related to neuronal maturation. Moreover, the locus encoding Cpg15/Neuritin (Nrn1), which is regulated by neuronal activity and implicated in stabilization and maturation of excitatory synapses, is a direct target of Ezh1 in cortical neurons. Together, these results suggest that elevated expression of Ezh1 contributes to maturation of cortical neurons.

  • I Ketut Gunarta, Dewi Yuliana, Purev Erdenebaatar, Yuhei Kishi, Jambal ...
    原稿種別: research-article
    2021 年 15 巻 2 号 p. 66-72
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/03/14
    ジャーナル フリー

    Curcumin, a major component of turmeric, is known to exhibit multiple biological functions including antitumor activity. We previously reported that the mitogen-activated protein kinase (MAPK) scaffold protein c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP) reduces curcumin-induced cell death by modulating p38 MAPK and autophagy through the regulation of lysosome positioning. In this study, we investigated the role of JNK/stress-activated protein kinase-associated protein 1 (JSAP1), a JLP family member, in curcumin-induced stress, and found that JSAP1 also attenuates curcumin-induced cell death. However, JSAP1 knockout showed no or little effect on the activation of JNK and p38 MAPKs in response to curcumin. In addition, small molecule inhibitors of JNK and p38 MAPKs did not increase curcumin-induced cell death. Furthermore, JSAP1 depletion did not impair lysosome positioning and autophagosome-lysosome fusion. Instead, we noticed substantial autolysosome accumulation accompanied by an inefficient autophagic flux in JSAP1 knockout cells. Taken together, these results indicate that JSAP1 is involved in curcumin-induced cell death differently from JLP, and may suggest that JSAP1 plays a role in autophagosome degradation and its dysfunction results in enhanced cell death. The findings of this study may contribute to the development of novel therapeutic approaches using curcumin for cancer.

  • Kazuhiro Mikami, Kazunari Sonobe, Keiko Ishino, Takumi Noda, Mami Kato ...
    原稿種別: research-article
    2021 年 15 巻 2 号 p. 73-77
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/04/29
    ジャーナル フリー

    Nocardia is a ubiquitous environmental microbe that causes nocardiosis against immunosuppressed and immunocompromised hosts. The assay system for the quantitative evaluation of virulence of Nocardia sp. or therapeutic effectiveness of antimicrobials for treatment of nocardiosis is not established so far. In this study, we established an infection model of Nocardia sp. using silkworm as an alternative animal model. We found that all tested Nocardia sp. such as Nocardia asiatica, Nocardia elegans, Nocardia exalbida, Nocardia farcinica, and Nocardia nova killed silkworm and their killing ability were different by species. N. farcinica showed higher pathogenicity among tested strain, similar to the mouse model as previously reported. In addition, we found that antimicrobials such as amikacin and minocycline showed therapeutic effectiveness in silkworms infected with N. farcinica, and we could determine effective doses 50 (ED₅₀) values. These results suggest that silkworm is a useful alternative animal to evaluate the pathogenicity of Nocardia pathogen and the therapeutic effects of antimicrobials against Nocardia sp. in a quantitative manner.

  • Mao Kunimitsu, Yukie Kataoka, Gojiro Nakagami, Carolina D. Weller, Hir ...
    原稿種別: research-article
    2021 年 15 巻 2 号 p. 78-86
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/04/30
    ジャーナル フリー

    All open wounds are often colonized by commensal microbes as a loss of skin can provide a ready portal of entry for microorganisms. Although the wound microbiota is known to be associated with wound infection and with delayed healing, the factors related to the formations of wound microbiota contributing to such poor clinical outcomes are not clear and have not led to effective infection prevention interventions. This review aimed to scope the factors related to the composition and diversity of wound microbiota that have been investigated using culture-independent molecular methods. Original articles on wound microbiota published from January 1986 to February 2020 were included in this review. Thirty-one articles met the inclusion criteria and were grouped according to wound types: chronic, acute, and animal model wounds. The factors identified were categorized according to patient characteristics, wound characteristics, treatment, and sampling. Although some studies reported the effect size of the factors, the values were small. No studies elucidated the mechanism of wound microbiota formation. The results of this scoping review highlight that the factors associated with the diversity of wound microbiota are poorly understood and that further studies are needed.

  • Mitsuru Nozawa, Miho Goto, Yuko Wada, Fumiyoshi Ishii, Ken-ichi Shimok ...
    原稿種別: research-article
    2021 年 15 巻 2 号 p. 87-92
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/04/29
    ジャーナル フリー

    Tape products containing ketoprofen have transdermal analgesic and anti-inflammatory effects. We compared the physicochemical properties (water-vapor permeability, peel force, peel force-time curve) between one brand-name product and eight generic products. Regarding the measurement of water-vapor permeability, the formulations using methacrylic acid n-butyl acrylate copolymer (MBA) adhesives showed higher water-vapor permeability than those using styrene isopropyl styrene block copolymer (SIS) adhesives. In the case of the formulation using SIS adhesive, the central part of the formulation had higher water-vapor permeability than both ends. In the 90-degree peel test using the methods of adhesion testing, significant differences were observed between the products, especially as the various application times (5 min, 30 min, 9 h and 24 h) increased. This may be because the longer the time of attachment to the adherend, the more the adhesive force with the adherend increased due to the "anchoring effect" of the adhesive. The measurement of the peel force-time curve showed different curves among the products, especially in the peel force curve of Teikoku after 24 h, which showed two characteristic peak curves. Furthermore, when the peel forces at 25°C and 40°C were compared, Mohrus and Toko showed significantly higher values at 40°C compared to 25°C. This study showed that there are many generic drugs with formulation characteristics different from those of brand-name drugs, and that there is a large difference among the products in terms of adhesion and detachment.

  • Sho Nishiguchi, Nagisa Sugaya, Yusuke Saigusa, Masahiko Inamori
    原稿種別: research-article
    2021 年 15 巻 2 号 p. 93-100
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/04/29
    ジャーナル フリー

    As end-of-life (EOL) care in nursing homes is gradually increasing, interprofessional collaboration in EOL care in nursing homes is becoming important. However, a method for measuring interprofessional collaboration has not been established. Therefore, this study aimed to clarify the effect of interprofessional collaboration on EOL care in nursing homes. Questionnaires were mailed to the facility directors of 378 nursing homes in Kanagawa Prefecture, Japan, and distributed to nurses, care managers, and professional caregivers. Three professionals from each nursing home completed the same questionnaire, which included 9 items on EOL care: shared facility policy, residents' wishes, each professional's roles, person in charge of the facility, residents' conditions, mental status of residents' families, emergency codes, residents' key people, and sufficient discussion among professionals. Based on the professionals' responses, interprofessional collaboration was assessed. We used multivariable analysis, with interprofessional collaboration as an independent factor. The outcome was the amount of EOL care in the nursing home. A total of 180 (47.6%) nursing homes participated. Multivariable analysis showed that interprofessional collaboration (beta [β] coefficient 2.5, 95% confidence interval [CI] 0.45-4.48; p = 0.017), availability of EOL care bonuses (β coefficient 4.4, 95% CI 1.41-7.38; p = 0.004), physician support for emergency care during off time (β coefficient 5.4, 95% CI 1.86-8.94; p = 0.003), and EOL care conferences (β coefficient 4.1, 95% CI 1.19-6.99; p = 0.006) were significant factors associated with the amount of EOL care in the nursing homes. We found evidence in the adjusted model that interprofessional collaboration among facility professionals is effective for EOL care in nursing homes.

  • Akiko Yaguchi-Saito, Ken Yamamoto, Tami Sengoku, Machi Suka, Tsugumich ...
    原稿種別: research-article
    2021 年 15 巻 2 号 p. 101-107
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/04/30
    ジャーナル フリー

    Since 2011, pharmaceutical companies in Japan have been required to issue two types of documents regarding severe adverse drug reactions reported post-marketing, namely the Rapid Safety Communication Materials for Patients and the Related Materials. However, the adequacy of these documents has not yet been systematically assessed. The aim of this study was to evaluate the adequacy of these two types of materials. The Rapid Safety Communications for Patients were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. The Related Materials were obtained from pharmaceutical companies or the PMDA website. Three assessors independently scored the Rapid Safety Communication for Patients and the Related Materials using the Centers for Disease Control and Prevention Clear Communication Index (CCI). In addition, the contents and descriptions of the materials were analyzed. In total, 13 materials for seven drugs were assessed. Almost all materials contained the "main message" and "call to action". However, the average CCI scores for the Rapid Safety Communication for Patients and Related Materials for Patients were 68.8 and 74.3 (out of 100), respectively. Further, none of the evaluated materials were scored above the CCI threshold score (i.e., ≥ 90%). Descriptions regarding "language", "state of science", and "risk" were not adequate. In particular, the terminology used in materials seemed difficult for patients to understand. In conclusion, the Japanese Rapid Communication Materials for Patients require improvement. Furthermore, a system for evaluating these materials prior to publication should be established.

Brief Report
  • Yusuke Morinaga, Kouhei Nii, Hayatsura Hanada, Yusuke Takemura, Kimiya ...
    原稿種別: brief-report
    2021 年 15 巻 2 号 p. 108-111
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/04/29
    ジャーナル フリー

    Barré-Lièou syndrome (BLS) is a manifestation of various autonomic and secondary symptoms including muscle stiffness, tinnitus, dizziness, and pain in various body parts. Although considered to be caused by hyperactivation of the autonomic nervous system due to trauma, there is currently no firmly established etiology or evidence on the treatment and clinical features of BLS. We retrospectively examined the clinical features of BLS and evaluated the efficacy of trazodone (TZD) for its treatment. We conducted a retrospective analysis of the data of 20 consecutive cases with suspected BLS who were treated in our hospital between 2016 and 2019. BLS symptoms were rated on a 10-point scale, and two groups were defined, that is, a mild-BLS group (BLS scores, 1-5) and a severe-BLS group (BLS scores, 6-10). Univariate analysis of patient factors was performed. The BLS score was 6.0 ± 1.7, and the maximum TZD dose was 80 ± 34 mg/day; nine patients (45%) were TZD free, and no TZD side effects were observed, while all patients had a good clinical outcome. There were significant differences between the mild-BLS and severe-BLS groups in the period from injury to diagnosis (p = 0.015), chest/back pain (p < 0.001), constipation (p = 0.001), and maximum TZD dose (p = 0.008). BLS involves posttraumatic autonomic symptoms accompanied by depression and insomnia. The sympathetic hypersensitivity theory could explain its etiology. TZD could effectively and safely treat BLS, and early diagnosis and treatment can contribute toward good clinical outcomes. Enhanced recognition and understanding of this disease are warranted.

Case Report
  • Menghua Zhu, Hongyu Li, Chunhui Wang, Benqiang Yang, Xuehan Wang, Feif ...
    原稿種別: case-report
    2021 年 15 巻 2 号 p. 112-117
    発行日: 2021/04/30
    公開日: 2021/05/11
    [早期公開] 公開日: 2021/04/29
    ジャーナル フリー

    Focal nodular hyperplasia (FNH) is a solid benign tumor of the liver, predominantly in young women. A correct diagnosis of FNH is essential for making appropriate clinical decisions and avoiding unnecessary liver resection. Herein, we reported that two male cases with FNH, who initially presented with persistent abdominal discomfort, were misdiagnosed with hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) on contrast-enhanced magnetic resonance imaging and computed tomography scans, respectively. After surgery, a histological diagnosis of FNH was finally established. In this paper, we also reviewed the knowledge regarding diagnosis and differential diagnosis of FNH on imaging examinations, which are helpful for avoiding misdiagnoses and guiding clinical interventions.

Erratum
feedback
Top