Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
早期公開論文
早期公開論文の10件中1~10を表示しています
  • Dazhuang Huang, Daijiro Haba, Sanai Tomida, Chihiro Takizawa, Qi Qin, ...
    論文ID: 2025.01061
    発行日: 2025年
    [早期公開] 公開日: 2025/08/28
    ジャーナル フリー 早期公開

    Diabetic foot ulcers (DFUs) are associated with a high risk of amputation and mortality, necessitating effective wound-healing interventions. Low-frequency vibration (LFV) therapy promotes wound healing by increasing glucose metabolism; however, the mechanisms underlying the effects of LFV on glucose metabolism remain unclear. This study aimed to investigate the role of Piezo1 in glucose uptake induced by LFV in adipocytes. 3T3-L1 adipocytes were subjected to LFV (52 Hz, 600–1,000 mVpp, and 40 min/day) for five days. Cells were divided into non-LFV and LFV groups, both with or without the Piezo1 inhibitor, which was evaluated for intracellular (Ca2+) fluorescence intensity, glucose transporter 4 (GLUT4) localization, and glucose uptake. The increased intracellular Ca2+ fluorescence intensity induced by LFV was significantly attenuated when combined with Piezo1 inhibitor (p < 0.0001). LFV-induced GLUT4 translocation to the plasma membrane was canceled, and glucose uptake was significantly decreased in the LFV group treated with Piezo1 inhibitor (p < 0.001) compared to the LFV group without Piezo1 inhibitor. The activation of Piezo1 by LFV may lead to a cascade involving Ca2+ influx, GLUT4 translocation, and increased glucose uptake. These findings suggest that Piezo1 plays a critical role in promoting the glucose uptake induced by LFV in adipocytes.

  • Feijun Ye, Yanlin Zhang, Ziqin Chen, Jing Zhou, Jing Wang, Xiayan Fu, ...
    論文ID: 2025.01067
    発行日: 2025年
    [早期公開] 公開日: 2025/08/28
    ジャーナル フリー 早期公開

    This meta-analysis summarizes the differences in serum lipid levels among postmenopausal women with osteopenia, osteoporosis, and normal bone mass, aiming to establish reliable lipid markers for predicting bone loss in postmenopausal women. Relevant literature published up to March 21, 2024, was sourced from databases including PubMed, Embase, Web of Science, and the Cochrane Library. Following a thorough evaluation in accordance with established inclusion and exclusion criteria, the meta-analysis incorporated 14 studies, involving a total of 12,974 postmenopausal women. The weighted mean deviation (WMD) and 95% confidence intervals (CIs) were conducted by RevMan 5.4 software. The findings indicated that serum triglyceride (TG) concentrations were significantly lower in osteopenia (WMD = -6.82, 95% CI: -9.80 to -3.83, P = 0.05, I2 = 42%) and osteoporosis (WMD = -10.28, 95% CI: -14.51 to -6.04, P < 0.001, I2 = 45%) women compared to their normal counterparts. In addition, serum high-density lipoprotein cholesterol (HDL-C) levels were notably elevated in osteoporosis women (WMD = 1.66, 95% CI: 0.75 to 2.57, P = 0.0004, I2 = 43%). However, no significant discrepancies were found in total cholesterol and low-density lipoprotein cholesterol levels among postmenopausal women with bone loss. Sensitivity analysis showed that the results of the meta-analysis were reliable. Egger's test showed no publication bias in the included studies. Consequently, our meta-analysis shows that low serum TG levels predict the onset of osteopenia in postmenopausal women, while high serum HDL-C levels suggest a potential risk for osteoporosis.

  • Ryoken Aoki, Kentaro Ishido, Megumi Furukawa, Yukiko Ishibashi, Shotar ...
    論文ID: 2025.01047
    発行日: 2025年
    [早期公開] 公開日: 2025/08/26
    ジャーナル フリー 早期公開

    Lactoferrin, a multifunctional protein found in breast milk, is important for the regulation of immune function. Non-alcoholic steatohepatitis (NASH), which is characterized by hepatitis and fibrosis, has no established drug treatment. In this study, we aimed to investigate the effects of lactoferrin on hepatocyte inflammation in a mouse model of NASH induced with a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). As a method, C57BL/6JJmsSlc mice were fed CDAHFD for 14 days and simultaneously intake lactoferrin (3.3 g/kg or 6.6 g/kg) of water. Then, plasma levels aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were measured and gene expression levels of inflammatory cytokines in the liver were examined. Plasma levels of ALT and AST significantly increased in the NASH model, indicating hepatocyte inflammation, and lactoferrin intake suppressed their elevation in a dose-dependent manner. Histological analysis revealed that lactoferrin alleviated the fatty liver-associated tissue damage. Additionally, lactoferrin suppressed the gene expression of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin (IL)-1β, and IL-6 and the macrophage migration factor (MCP)-1, suggesting inhibition of macrophage activation. Lactoferrin also significantly reduced the expression of apoptosis-related genes (caspase 3 and p53), indicating its anti-apoptotic effects. Furthermore, lactoferrin alleviated oxidative stress by suppressing inducible nitric oxide synthase expression. These findings suggest that lactoferrin prevented liver injury in the mouse model of NASH induced by CDAHFD feeding by inhibiting macrophage-mediated inflammation and alleviating oxidative stress caused by fat accumulation.

  • Yuma Nonomiya, Masashi Nakamura, Tomonori Nakamura, Masakazu Yamaguchi
    論文ID: 2025.01063
    発行日: 2025年
    [早期公開] 公開日: 2025/08/26
    ジャーナル フリー 早期公開

    Since 2022, the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR) has participated in a postgraduate clinical training program organized by the Japanese Society of Hospital Pharmacists. Subsequently, the training system for newly employed pharmacists was reviewed. Beginning in 2023, a structured lecture-based training program was introduced for young pharmacists (employees in their first to fifth years of practice). To evaluate the effectiveness and usefulness of the newly implemented lecture-based training program (LBTP), a questionnaire survey was conducted using open-ended and multiple-choice questions based on a 5-point Likert scale. The lectures were conducted with the participation of 12 individuals, all of whom had less than five years of professional experience. All lectures received high ratings in terms of content and the participants’ level of understanding, suggesting a high degree of overall satisfaction. Furthermore, after the lectures, the lecturers reported an increased understanding of the lecture-based training program and expressed their willingness to contribute actively in the following fiscal year. Both the participants and lecturers reported high levels of satisfaction, demonstrating the usefulness of the program. As the JFCR is a cancer-specialized hospital, there is a need for more proactive learning on topics beyond oncology. The LBTP had a positive impact on both participants and lecturers, contributing to the enhancement of education for new staff members.

  • Zhiying Qiu, Liang Fang, Shaojie Li, Jianxiong Tang, Yun Pang, Jing Wa ...
    論文ID: 2025.01066
    発行日: 2025年
    [早期公開] 公開日: 2025/08/26
    ジャーナル フリー 早期公開

    The aim of this study was to compare postoperative complications and long-term clinical efficacy of electrospun composite biomaterial and porcine small intestine submucosa (SIS) patch in open inguinal herniorrhaphy. A prospective, randomized, single-blind, controlled, multicenter study was used to select 172 patients with inguinal hernia who met the inclusion criteria in 3 hospitals. All participants were randomly assigned (1:1) and treated by open inguinal herniorrhaphy. The experimental group used electrospun composite biomaterial patch and the control group used SIS patch. Complications were assessed by ultrasonic volume auto-scan (UVAS) at 6, 33 and 72 months after operation. The results showed that 53 cases were found to be positive by UVAS, including 20 cases of encapsulated effusion (12.74%), 11 cases of soft tissue edema (6.40%), 4 cases of recurrence (3.01%), 2 cases of testicular ischemic atrophy (1.50%), 7 cases of testicular hydrocele (5.26%), 6 cases of varicocele (4.51%), 2 cases of spermatic cord cyst (1.27%) and 1 case of epididymal head cyst (0.64%). At 33-month follow-up, 2 cases recurred in the control group (2/79, 2.53%) while none in the experimental group (0/78) (the 95% CI difference in effective rates between the two groups was -0.93% to 6.00%, within the preset non-degradation range of Δ10%). At 72-month follow-up, there were 4 cases of recurrence in the control group (4/59, 6.78%), while none in the experimental group (0/60) (the lower limit of 95% CI difference in effective rates between the two groups was 0.27% > 0). The main clinical efficacy of the experimental group was better than that of the control group. There was no statistical difference in the secondary efficacy between the two groups. The postoperative safety evaluation effect of the two groups was the same. Long-term follow-up with UVAS after operation showed that the main clinical efficacy of electrospun composite biomaterial applied in this procedure was superior to that of SIS patch, and there was no significant difference in the secondary efficacy between the two biological patches.

  • Guimei Zhang, Qi Wang, Li Zhao, Hao zhang, Jie Lin, Tetsuya Asakawa
    論文ID: 2025.01068
    発行日: 2025年
    [早期公開] 公開日: 2025/08/26
    ジャーナル フリー 早期公開

    The aim of this study was to investigate the value of an Internet of things (IOT)-aided warehouse management system (IAWMS) to improve the efficiency of consumables management for the operating room (OR). Indices in three domains (error alerts, time taken for work, and level of satisfaction) were selected. Records were compared for two groups, namely the IAWMS group (records after implementation of IAWMS from March 2024 to September 2024) and the control group (manual work before implementation of IAWMS from July 2023 to December 2023). Results revealed that the IAWMS significantly reduced error alerts and the time taken for routine work. The level of satisfaction of the medical staff improved significantly. Noticeably, the time taken to conduct a physical inventory decreased markedly (12.57 ± 1.27 min vs. 840.00 ± 120.00 min, p < 0.0001). This pilot study confirmed the value of an IAWMS in improving the operational efficiency of consumables management for the OR in a Chinese setting. The IAWMS relieves medical staff from heavy manual work. Thus, the IAWMS is recommended for routine management of consumables for the OR.

  • Natsuki Oshima, Akiho Yagi, Hiroyuki Yamazaki, Ryuji Uchida
    論文ID: 2025.01052
    発行日: 2025年
    [早期公開] 公開日: 2025/08/24
    ジャーナル フリー 早期公開

    To examine the potential of nucleoside antibiotics as therapeutic agents against Mycobacterium avium complex (MAC), the in vitro and in vivo anti-MAC activities of streptcytosine A (1), plicacetin (2), and bamicetin (3) derived from a marine actinomycete were evaluated. Compounds 13 exhibited antimicrobial activities against M. avium and M. intracellulare, with minimum inhibitory concentration values of 4.0 and 16 μg/mL, respectively, as assessed by the microdilution method. In silkworm infection models of M. avium and M. intracellulare, these compounds also exhibited therapeutic efficacies at lower doses than clarithromycin, with 50% effective doses of between 7.6 and 28 μg/larva·g, and no toxicity was observed. A pharmacokinetic analysis further revealed elimination half-lives of 3.0, 2.3, and 5.1 hours, respectively, in the silkworm hemolymph. These results suggest the potential of 13 as lead candidates for the development of potent anti-MAC drugs.

  • Ryo Okuyama
    論文ID: 2025.01056
    発行日: 2025年
    [早期公開] 公開日: 2025/08/23
    ジャーナル フリー 早期公開

    Japan's international competitiveness in biomedical innovation is declining, as evidenced by its expanding trade deficit in pharmaceuticals. One reason for this is that the ecosystem connecting academic research outcomes to startups and new businesses, and promoting commercialization and industrial applications is not functioning adequately. Recently, the Japanese government has implemented policy measures to revitalize biomedical ecosystems. This study reviews the current state and characteristics of the biomedical ecosystems in Japan. Several biomedical ecosystems, both with and without geographic concentration, have been established and operated over the past 25 years, most of which are relatively small-scale and driven by governments. Recently, the Japanese government has aimed to form larger biocommunities, including biomedical innovations, to expand the bioeconomy. This study discusses these policy initiatives and their associated challenges. Furthermore, it outlines recent government initiatives to strengthen the drug discovery ecosystem, which focuses on attracting talent, companies, and new drug developers from overseas. Based on these analyses, this study addresses the challenges faced by Japan's biomedical ecosystem and discusses future directions.

  • Toshimasa Shimizu, Shin-ya Kawashiri, Tomohiro Koga, Rieko Kiya, Michi ...
    論文ID: 2025.01044
    発行日: 2025年
    [早期公開] 公開日: 2025/08/22
    ジャーナル フリー 早期公開

    Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by the presence of autoantibodies, with infliximab (IFX), the first biological disease-modifying anti-rheumatic drug (DMARD) targeting tumor necrosis factor α, significantly improving treatment but prompting the development of cost-effective biosimilar DMARDs due to its high cost. This study aimed to investigate the efficacy and safety of switching from originator to biosimilar IFX, CT-P13, in patients with RA using musculoskeletal ultrasound (MSUS) and clinical disease activity indices. This prospective, open-label, interventional, single-arm clinical trial involved a 24-week follow-up, enrolling patients with RA who had achieved clinical remission during treatment with originator IFX. CT-P13 was switched from the originator IFX with an unchanged dosing regimen for 24 weeks. The study utilized not only clinical disease activity indices but also MSUS and serum cytokines/chemokines. Eighteen patients were evaluated during the study period. From baseline to week 24, two of the 18 patients experienced clinical relapse (11.1% [95% CI: 3.1–32.8]). No changes were observed in the MSUS score, including total grayscale and power Doppler scores, Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate, DAS28-C-reactive protein, Health Assessment Questionnaire-Disability Index, and van der Heijde-modified total Sharp score from baseline to week 24. Serum levels of multiple cytokines/chemokines showed no apparent changes. Three non-serious adverse events occurred, with no study discontinuations due to adverse events. In conclusion, most RA patients undergoing treatment with originator IFX in clinical remission could safely switch to CT-P13 without an increased risk of relapse, as evidenced by MSUS, clinical indices, and biomarker levels.

  • Chenru Zhao, Daoran Lu, Jianjun Gao
    論文ID: 2025.01058
    発行日: 2025年
    [早期公開] 公開日: 2025/07/11
    ジャーナル フリー 早期公開

    Telisotuzumab vedotin represents a clinically important antibody-drug conjugate (ADC) that received accelerated approval from the US Food and Drug Administration in May 2025, establishing it as the first-in-class targeted therapy for adult patients with immunohistochemistry (IHC)-confirmed high-c-Met, EGFR wild-type, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Its mechanism of action relies on precise targeting of the c-Met protein receptor, followed by internalization and release of the potent cytotoxic payload monomethyl auristatin E (MMAE) to eradicate tumor cells. The pivotal phase II LUMINOSITY trial demonstrated that the high c-Met overexpressing group had an overall response rate (ORR) of 34.6%. This therapeutic agent addresses a critical unmet need within a molecularly defined NSCLC subpopulation, marking a substantial advancement in c-Met-targeted oncology. The regulatory authorization and clinical use of telisotuzumab vedotin may significantly advance precision medicine for NSCLC, though an ongoing phase III trial will further confirm its efficacy and safety and determine its eligibility for full regulatory approval in the future.

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