Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
Current issue
Displaying 1-9 of 9 articles from this issue
Original Article
  • Atsushi Miyashita, Kazuhiro Mikami, Hiroto Nakajima, Yidong Yu, Masano ...
    2025 Volume 19 Issue 2 Pages 83-89
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    Advance online publication: April 27, 2025
    JOURNAL FREE ACCESS

    Aeromonas hydrophila is a significant pathogenic bacterium in aquaculture and the ornamental fish industry, causing lethal infections in fish and contributing to rising drug resistance. This leads to substantial economic losses and underscores the urgent need for new treatments and infection controls. However, the lack of a simple, sensitive infection model has hindered studies on the pathogenicity of A. hydrophila and therapeutic evaluation. This study introduces the silkworm (Bombyx mori) as a highly sensitive and cost-effective infection model for A. hydrophila. Using a strain isolated from diseased Wakins (goldfish), the pathogenicity of A. hydrophila was confirmed in silkworms, which exhibited a much lower median lethal dose (LD₅₀ = 0.3 CFU/larva) compared to Wakins (LD₅₀ = 5.1 × 10⁶ CFU/g body weight). This demonstrates the silkworm's higher sensitivity to A. hydrophila. The in vivo efficacy of three antibiotics (gentamicin, kanamycin, and tetracycline) was also tested. Gentamicin and kanamycin prolonged survival in both models, while tetracycline also showed efficacy in both models, though its effect was weaker in the silkworm model. This highlights the silkworm model's utility in evaluating bactericidal agents against A. hydrophila. This model addresses key limitations of traditional fish infection models, including low sensitivity, long experimental durations, and high costs. The silkworm-based method enables efficient investigation of A. hydrophila pathogenicity and rapid screening of potential treatments, accelerating the development of new therapeutic strategies for aquaculture and beyond.

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  • Shingo Kondo, Ririka Mima, Rira Okui, Hiroki Iwata, Yoshiko Kawamoto, ...
    2025 Volume 19 Issue 2 Pages 90-95
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    Advance online publication: April 27, 2025
    JOURNAL FREE ACCESS

    Expectations for pharmacists' contribution and involvement in pressure ulcer pharmacotherapy are growing. This study aimed to not only clarify the effects of incorporating practical training on the use of topical medications into clinical preparatory education but also examine the relationship between students' aspiration—or lack thereof—to pursue a career as a pharmacist. The percentage of positive responses to the questionnaire survey on knowledge, skills, and attitudes toward pressure ulcer treatment was significantly higher after the lecture than before and highest after the practical training. In addition, students who aspired to become pharmacists tended to provide a higher percentage of positive responses after the lecture. However, the gap between aspiring and non-aspiring pharmacists tended to narrow after practical training. These results suggest that incorporating practical training on pressure ulcer treatment into lectures improves students' knowledge, skills, and attitudes toward its treatment. Including practical training in pressure ulcer education may compensate for the difference in the educational effect of lectures between students who aspire to become pharmacists and those who do not, thereby improving the educational effect for the latter.

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  • Sayaka Yokoyama, Hana Kozai, Amane Kikuchi, Suzuno Ota, Takanori Horib ...
    2025 Volume 19 Issue 2 Pages 96-102
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    Advance online publication: April 27, 2025
    JOURNAL FREE ACCESS

    The aim of this study was to determine the time-dependent effects of the prickly pear (Nopalea cochenillifera) on the intestinal environment and immune function in BALB/c mice, which exhibit a predominant T helper 2 immune response. Five-week-old female BALB/c mice were divided into a control group and groups fed diets supplemented with 5% or 10% N. cochenillifera powder (NCP). Blood and feces were collected every 7 days. On day 28, in addition to blood and feces, the small intestine, cecum, and large intestine were collected. The cecum content weight, cecum content pH, and fecal mucin were examined. Serum antibody levels (total Immunoglobulin (Ig)M) were lower on days 14 and 21 in the 10% NCP group than in the control and 5% NCP groups. Total serum IgG levels were higher at all time points and total IgA levels were higher on days 7, 14, 21 and 28 in the 5% NCP and 10% NCP groups than in the control group. Total fecal IgA levels were lower in the 5% NCP and 10% NCP groups than in the control group from 14 days. Fecal mucin contents were higher in the 10% NCP group than in the control group from 7 days. These results suggest that N. cochenillifera supplementation exerts time-dependent effects on serum antibodies and the intestinal environment in BALB/c mice. In particular, NCP at 10% may enhance the intestinal mucosal barrier function and promote systemic immune responses. Further mechanistic studies are needed to determine the effects on immune responses.

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  • Yiding Yu, Yue Li, Jingyun Li, Xu Zhang, Xuemin Chen, Pengzhao Hu, Wen ...
    2025 Volume 19 Issue 2 Pages 103-111
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    Advance online publication: April 28, 2025
    JOURNAL FREE ACCESS

    Age-related hearing loss (ARHL) has been closely linked to genetic factors, with studies identifying the p.V37I mutation in the GJB2 gene as a potential contributor to ARHL. To investigate this, we generated a humanized p.V37I mutant mouse model and performed auditory brainstem response (ABR) testing, cochlear morphology assessments, and transcriptional sequence of mutant and wild-type (WT) mice at different ages. Our results indicated that this kind of GJB2 mutation does not lead to cochlear developmental abnormalities, and aging mutant mice exhibit only mild hearing loss compared to WT mice, without significant cochlear morphological differences. However, transcriptional analyses revealed substantial differences between mutant and WT mice. GO enrichment analysis of the DEGs between aging mutant and WT mice highlights significant enrichment in biological processes related to neural and sensory functions. Notably enriched terms include "neuron-to-neuron synapse," "immune response-activating signaling pathway," "regulation of synapse structure or activity," and "sensory perception of sound." These findings suggest that the p.V37I mutation in aging mice affects synaptic and calcium signaling pathways, as well as sensory system development. Despite these molecular changes, cochlear function remains normal in early life; however, as the mice age, hearing loss accelerates, likely due to a diminished capacity for gene-mediated protection against external stimuli.

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  • Xiang Zhang, Hongjing Guan, Xiaoyun Di, Mengqing Li, Jingli Peng, Rent ...
    2025 Volume 19 Issue 2 Pages 112-123
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    JOURNAL FREE ACCESS

    This study evaluated the impact of initiating antiretroviral therapy (ART) within 14 days compared to starting after 14 days in newly diagnosed, late-presenting people living with human immunodeficiency virus (PLWH). A total of 1,538 PLWH with a baseline CD4+ T-cell count < 350 cells/μL who attended our outpatient clinic from January 2017 to June 2022 were included. Participants were divided into two groups based on ART initiation timing: rapid initiation (ART within 14 days) and delayed initiation (ART after 14 days). Rapid initiation led to significantly higher virologic suppression rates at 6 months (62.5% vs. 52.7%, P < 0.05) and 1 year (81.6% vs. 72.1%, P < 0.01) compared to delayed initiation. While overall treatment retention rates were comparable, rapid initiation improved retention at 6 months for those with baseline CD4+ < 200 cells/μL and at 1 year for those with baseline CD4+ between 200 and 350 cells/μL. No significant differences in CD4+ T-cell counts or CD4/CD8 ratio were observed. A positive correlation was found between baseline viral load and time to virologic suppression, with rapid initiation of ART leading to faster suppression, especially in those with higher baseline viral loads. Multivariate analysis confirmed that ART initiation timing and baseline viral load were key determinants of virologic suppression. In conclusion, rapid ART initiation within 14 days was associated with higher virologic suppression at 6 months and 1 year. Rapid initiation of ART and lower baseline viral load were critical for virologic suppression, with improved retention for specific subgroups.

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Correspondence
  • Ya-nan Ma, Kenji Karako, Peipei Song, Ying Xia
    2025 Volume 19 Issue 2 Pages 124-128
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    JOURNAL FREE ACCESS

    Herpes Zoster (HZ), caused by the reactivation of the varicella-zoster virus (VZV), is a common infectious disease. Recent studies suggest a potential association between HZ and the development of dementia, particularly Alzheimer's disease and other neurodegenerative disorders. Epidemiological evidence indicates that HZ infection, especially in individuals with central nervous system involvement, may increase the risk of dementia. Pathologically, VZV may contribute to neuronal dysfunction and degeneration by inducing chronic neuroinflammation, infection-related cerebrovascular lesions, and direct central nervous system toxicity. HZ vaccines, particularly novel recombinant subunit vaccines (e.g., Shingrix), not only effectively prevent HZ but may also confer cognitive protection through mechanisms such as "trained immunity" activation and anti-inflammatory response modulation. Multiple natural experiments and retrospective cohort studies have found that HZ vaccination is significantly associated with a reduced risk of dementia, with particularly pronounced protective effects in women and older adults. Although most evidence currently stems from observational studies and is subject to potential confounding factors, the biological plausibility and consistent findings support the potential of HZ vaccination as an adjunctive strategy for dementia prevention. Future prospective randomized controlled trials are needed to further clarify the causal relationship and underlying neuroimmune mechanisms, providing a stronger evidence base for establishing scientific vaccination strategies for older adults and dementia prevention systems.

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  • Shasha Hu, Haizhou Yu, Jianjun Gao
    2025 Volume 19 Issue 2 Pages 129-130
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    Advance online publication: April 11, 2025
    JOURNAL FREE ACCESS

    Uncomplicated urinary tract infection (uUTI) is a common bacterial infection in women. While the condition typically has a favorable prognosis, the widespread use of antibiotics has led to increasingly bacterial resistance, reducing the efficacy of traditional antibiotics. On March 25, 2025, the US Food and Drug Administration approved gepotidacin for the treatment of uUTIs caused by susceptible bacteria in female adult and pediatric patients 12 years of age and older weighing at least 40 kg. Gepotidacin is the first triazaacenaphthylene antibiotic approved for clinical use. It selectively binds to and inhibits both bacterial DNA gyrase and topoisomerase IV, disrupting bacterial DNA replication through a unique mechanism and thereby killing the pathogen. Results of clinical trials indicated the non-inferiority of gepotidacin compared to the current standard therapy, nitrofurantoin. The most frequently reported adverse reaction to gepotidacin was mild to moderate diarrhea. The approval of gepotidacin represents a progress in antibiotic innovation, offering novel perspectives on drug development while spurring global efforts to tackle the escalating challenge of antimicrobial resistance.

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  • Daoran Lu, Fangzhou Dou, Jianjun Gao
    2025 Volume 19 Issue 2 Pages 131-132
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    Advance online publication: April 13, 2025
    JOURNAL FREE ACCESS

    Hemophilia is a coagulation disorder caused by deficiencies in clotting factors and is primarily classified into hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency). Current treatment relies predominantly on replacement therapy, where patients receive clotting factor concentrates either episodically or prophylactically to achieve hemostasis or mitigate bleeding risks. Despite its efficacy, this approach presents limitations, including suboptimal treatment accessibility due to high costs, reduced patient compliance from frequent intravenous administration, and therapeutic failure in patients developing plasma inhibitors. These challenges underscore the need for novel therapeutics addressing unmet clinical demands. On March 28, 2025, the US Food and Drug Administration (FDA) approved fitusiran, a small interfering RNA (siRNA) therapeutic for hemophilia. This first-in-class agent demonstrates pan-hemophilia efficacy by targeting antithrombin to enhance thrombin activity, irrespective of factor VIII/IX deficiency status or plasma inhibitor presence. By pioneering a mechanism of antithrombin suppression, enabling sustained therapeutic action, and facilitating precision monitoring protocols, fitusiran has the potential to redefine hemophilia treatment paradigms.

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  • Atsushi Ishimura, Yutaka Shimizu, Naohiro Yabuki
    2025 Volume 19 Issue 2 Pages 133-135
    Published: April 30, 2025
    Released on J-STAGE: May 09, 2025
    Advance online publication: April 27, 2025
    JOURNAL FREE ACCESS

    Glucagon-like peptide-1 receptor agonist (GLP-1RA) has attracted attention owing to its hypoglycemic and weight-loss effects, and various dosage forms are available in the market. Recently, glucose-dependent insulin secretion-stimulating polypeptide (GIP), an incretin hormone in the same family as GLP-1, has attracted attention, and tirzepatide, a GIP/GLP-1RA, has been launched. Given the short duration of tirzepatide on the market and the fact that its therapeutic effects in patients of different ages have not been reported, we conducted this study. HbA1c improved significantly in patients aged ≥ 65 years, whereas HbA1c, weight, and LDL cholesterol also improved significantly in patients aged ≤ 64 years when compared between the beginning of use and 3 months following use. Tirzepatide has a hypoglycemic effect regardless of age; however, its weight loss effect may be more pronounced in younger age groups. Therefore, optimal diabetes treatment with tirzepatide should consider the age and weight of patients.

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