Drug discoveries & therapeutics最新文献

{"title":"Tapeworm infection incidence in rural Japan points to a common environmental source of infection.","authors":"Dhammika Leshan Wannigama, Mohan Amarasiri, Phatthranit Phattharapornjaroen, Cameron Hurst, Yu Suzuki, Daisuke Akaneya, Mika Moriya, Taichi Adachi, Yoshikazu Okuma, Daisuke Ishizawa, Hitoshi Ishikawa, Kazuhiko Miyanaga, Longzhu Cui, Kazunori Moriya, Hirotake Mori, Naveen Kumar Devanga Ragupathi, Yoshitaka Shimotai, Daisuke Sano, Takashi Furukawa, Kazunari Sei, Talerngsak Kanjanabuch, Paul G Higgins, Tetsuji Aoyagi, Anthony Kicic, Sam Trowsdale, Parichart Hongsing, Aisha Khatib, Kenji Shibuya, Shuichi Abe, Hiroshi Hamamoto","doi":"10.5582/ddt.2025.01070","DOIUrl":"10.5582/ddt.2025.01070","url":null,"abstract":"<p><p>Dibothriocephalus nihonkaiensis is a zoonotic tapeworm transmitted to humans through consumption of raw or undercooked fish or wild meat. Between 2022 and 2023, Yamagata Prefecture reported an increase in cases compared with 2017-2021, when none were observed. We conducted a clinical and environmental investigation to clarify infection sources. Four confirmed and one suspected patient were identified, all presenting with gastrointestinal symptoms. Exposures were linked to raw cherry salmon (Oncorhynchus masou) in three cases and undercooked bear meat in one case. Praziquantel treatment (10-20 mg/kg) was effective, with eight worms (76-210 cm) recovered. Environmental surveillance detected D. nihonkaiensis in 33.3% of bear feces (20/60) and 21.8% of wild fish samples (17/78). Phylogenetic analysis showed close genetic relatedness among human, bear, and fish isolates, indicating a shared transmission cycle. These findings confirm zoonotic transmission of D. nihonkaiensis in Yamagata and highlight the need for food safety awareness and environmental monitoring.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"351-357"},"PeriodicalIF":0.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and reliability assessment of a liquid-phase measurement for skin taurine using skin blotting.","authors":"Katsunori Kato, Kazuhiro Ogai, Yoko Hasegawa, Chizuko Konya, Hiromi Sanada, Takeo Minematsu","doi":"10.5582/ddt.2025.01089","DOIUrl":"10.5582/ddt.2025.01089","url":null,"abstract":"<p><p>Skin taurine is an indicator of dehydration and can be noninvasively collected through skin blotting. However, conventional taurine measurement using ninhydrin raises safety and specificity concerns, limiting its application in point-of-care testing. In this study, we propose a novel liquid-phase measurement of taurine collected via skin blotting. The aim of this study was to develop a method for liquid-phase measurement of skin taurine and to demonstrate its validity and reliability. This study consisted of (1) determining optimal recovery conditions, including the type and concentration of recovery solution and shaking method (mild, intense, or no shaking), (2) evaluating the specificity of taurine measurement, and (3) assessing the intra- and inter-rater reliability of the developed method for skin taurine measurement. Optimal recovery was achieved by intense shaking for 10 min with a 110 mM sodium chloride solution, and this method could measure taurine concentrations from 31.25 to 500 μM (r = 0.9983, p < 0.001), confirming its validity. Linear regression analysis showed that the addition of amino acids or skin lysates had little effect on taurine measurement. The developed method demonstrated high intra-rater reliability (intraclass correlation coefficient [ICC] (1,1) = 0.896, p < 0.001 for examiner A; ICC (1,1) = 0.755, p < 0.001 for examiner B), but inter-rater reliability was not significant (ICC (2,1) = 0.187, p = 0.15). The liquid-phase measurement of skin taurine demonstrated high sensitivity, specificity, and intra-rater reliability. Further studies are needed to improve inter-rater reliability for applying this method as a point-of-care tool for dehydration assessment.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"314-324"},"PeriodicalIF":0.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food, medicine, and cosmetic homology: A comprehensive review of bioactive components, functions, and applications of Torreya grandis.","authors":"Xiaoyan Cui, Chuanyin Shi, Yan Sun","doi":"10.5582/ddt.2025.01092","DOIUrl":"10.5582/ddt.2025.01092","url":null,"abstract":"<p><p>Torreya grandis (T. grandis) is one of the evergreen tree species in China. The kernels of T. grandis have been used as traditional medicine and food for thousands of years in China. In recent years, it has also been developed as raw materials for cosmetics. T. grandis is rich in bioactive components, including unsaturated fatty acids, vitamins, protein, amino acids, trace elements, minerals, polyphenols, squalene, phytosterol, terpenes, etc. Therefore, T. grandis possesses a wide range of biological activities such as anti-oxidation, anti-inflammation, microbiota alteration, effects on blood pressure, blood glucose and lipids, neuroprotective effect, brightening, reducing uric acid (UA) level, ameliorating bone metabolism disorders, alleviating slow transit constipation, and antinociceptive activity. This review presents a comprehensive analysis of T. grandis on its active components and functions, and explores its existing and potential applications in food, medicine, and cosmetics.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"294-303"},"PeriodicalIF":0.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solid phase extraction and high-performance liquid chromatographic determination of lazertinib in human plasma.","authors":"Yoshito Gando, Takeo Yasu","doi":"10.5582/ddt.2025.01077","DOIUrl":"10.5582/ddt.2025.01077","url":null,"abstract":"<p><p>Lazertinib is a novel third-generation tyrosine kinase inhibitor (TKI) developed for the treatment of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Reports on previous EGFR-TKIs have detailed significant associations between blood drug concentration and efficacy. In addition, significantly elevated blood concentrations of lazertinib have been observed in Asians compared to Caucasians, suggesting the influence of interethnic variability. In this study, we developed and validated a method to determine lazertinib concentrations in human plasma for therapeutic drug monitoring (TDM). Lazertinib and its internal standard, sotorasib, were extracted by solid-phase extraction using an Oasis hydrophilic lipophilic balance cartridge. Chromatographic separation was performed on a reversed-phase column with 0.5% KH₂PO₄ (pH 4.5) and acetonitrile (52:48, v/v) as the mobile phases in an isocratic elution mode with a flow rate of 1.0 mL/min. The detection wavelength was 296 nm. The calibration curves were linear in the range of 25-2,000 ng/mL, with a coefficient of determination (r²) of 0.9997. The accuracy and precision of all validation experiments were within the criteria set by the Food and Drug Administration guidelines. This study represents the first development and validation of a method for quantifying lazertinib in human plasma. This study is expected to facilitate the widespread use of TDM in studies on lazertinib.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"346-350"},"PeriodicalIF":0.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing epidemiology of respiratory pathogens since 2020: Shenzhen case study and global perspectives.","authors":"Chun Chen, Houming Liu, Jiaye Liu, Peifen Chen, Hongzhou Lu","doi":"10.5582/ddt.2025.01108","DOIUrl":"10.5582/ddt.2025.01108","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic fundamentally disrupted global respiratory virus epidemiology through widespread non-pharmaceutical interventions. Analysis of a tertiary hospital in Shenzhen (2021-2024) reveals profound alterations in seasonal patterns. Influenza A exhibited multiple atypical peaks including summer circulation, while influenza B showed delayed resurgence with sustained winter activity. Respiratory syncytial virus demonstrated altered seasonality with substantial warm-season transmission replacing traditional winter patterns. World Health Organization (WHO) global surveillance confirmed parallel worldwide trends. Influenza activity collapsed dramatically in 2021 before resurging with irregular timing and unprecedented intensity through 2025. Respiratory syncytial virus exhibited off-season epidemics across multiple regions before gradually re-establishing modified seasonal patterns at elevated baseline levels. These epidemiological shifts resulted from immunity gaps created by reduced viral exposure, staggered lifting of pandemic restrictions across regions, and viral competition dynamics. Emerging technologies including AI-driven prediction models, expanded wastewater surveillance systems, and universal vaccine development offer promising approaches for managing future respiratory disease dynamics in this evolving post-pandemic landscape.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"277-284"},"PeriodicalIF":0.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Mycobacterium avium complex activities of streptcytosine analogs from a marine actinomycete as nucleoside antibiotics.","authors":"Natsuki Oshima, Akiho Yagi, Hiroyuki Yamazaki, Ryuji Uchida","doi":"10.5582/ddt.2025.01052","DOIUrl":"10.5582/ddt.2025.01052","url":null,"abstract":"<p><p>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 1-3 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 1-3 as lead candidates for the development of potent anti-MAC drugs.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"262-266"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telisotuzumab vedotin: The first-in-class c-Met-targeted antibody-drug conjugate granted FDA accelerated approval for treatment of non-squamous non-small cell lung cancer (NSCLC).","authors":"Chenru Zhao, Daoran Lu, Jianjun Gao","doi":"10.5582/ddt.2025.01058","DOIUrl":"10.5582/ddt.2025.01058","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"275-276"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bovine lactoferrin intake prevents hepatic injury in a mouse model of non-alcoholic steatohepatitis induced by choline and methionine deficiency.","authors":"Ryoken Aoki, Kentaro Ishido, Megumi Furukawa, Yukiko Ishibashi, Shotaro Nozaki, Neon Ito, Masahiro Toho, Daichi Nagashima, Nobuo Izumo","doi":"10.5582/ddt.2025.01047","DOIUrl":"10.5582/ddt.2025.01047","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"230-236"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revitalizing Japan's biomedical ecosystem: Policy initiatives, challenges, and future directions.","authors":"Ryo Okuyama","doi":"10.5582/ddt.2025.01056","DOIUrl":"10.5582/ddt.2025.01056","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"214-219"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switching from originator infliximab to biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving clinical remission (the IFX-SIRIUS study I): An interventional, multicenter, open-label, single-arm clinical trial with clinical, ultrasound and biomarker assessments.","authors":"Toshimasa Shimizu, Shin-Ya Kawashiri, Tomohiro Koga, Rieko Kiya, Michiko Morita, Shohei Kuroda, Shigeki Tashiro, Shuntaro Sato, Hiroshi Yano, Tomoyuki Asano, Kazuyoshi Saito, Tamami Yoshitama, Yukitaka Ueki, Nobutaka Eiraku, Yutaro Yamada, Tadashi Okano, Yusuke Ushio, Hiroaki Dobashi, Tetsu Itami, Daisuke Tomita, Yuji Nozaki, Naoki Hosogaya, Hiroshi Yamamoto, Atsushi Kawakami","doi":"10.5582/ddt.2025.01044","DOIUrl":"10.5582/ddt.2025.01044","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":520606,"journal":{"name":"Drug discoveries & therapeutics","volume":" ","pages":"253-261"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}