Translational and Regulatory Sciences
Online ISSN : 2434-4974
Current issue
Displaying 1-7 of 7 articles from this issue
FULL PAPER
  • Yusuke MAEDA, Shota KUBOTA, Mai KAMIMURA, Hiroki OKUYAMA, Moe NISHIDA, ...
    2025Volume 7Issue 2 Pages 46-56
    Published: 2025
    Released on J-STAGE: August 20, 2025
    Advance online publication: July 30, 2025
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    Supplementary material

    Narrowband ultraviolet radiation (NB-UVR) phototherapy is widely used to treat various skin diseases such as atopic dermatitis and psoriasis. Although the mechanisms of NB-UVR at doses exceeding the minimal erythema dose (MED) have been extensively studied, the mechanisms of sub-MED irradiation remain unclear. This study investigated the effects of NB-UVR on naturally occurring canine atopic dermatitis and analyzed the underlying mechanisms of sub-MED irradiation using in vivo and in vitro canine models. Clinically, NB-UVR irradiation at 310 and 320 nm improved lesion scores, with a significant effect observed with low-dose 320 nm irradiation (n=6, P<0.05). To compare the effects of sub-MED of NB-UVR wavelengths (310, 320, and 330 nm), intradermal skin tests in experimental beagles showed significant alleviation of anaphylactoid reactions across all wavelengths (n=3, P<0.01). The number of cutaneous mast cells was significantly reduced following 310 nm irradiation (n=3, P<0.05). In vitro, WST assays and DAPI staining demonstrated reduced cell viability at 310 and 320 nm (P<0.01), with apoptosis specifically induced at 310 nm (P<0.01). RNA sequencing identified differentially expressed genes associated with muscle cell components and function after 320 nm exposure (n=3, q<0.1). These findings suggest that sub-MED NB-UVR, especially at 320 nm, may offer non-erythemogenic and safer phototherapy, with potential benefits for skin repair.

SHORT COMMUNICATION
  • Noriko HASHIBA, Yuzhe YUAN, Emi ITO-KUDO, Kyoko MASUMI-KOIZUMI, Keisuk ...
    2025Volume 7Issue 2 Pages 57-62
    Published: 2025
    Released on J-STAGE: August 20, 2025
    Advance online publication: April 24, 2025
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    Large-scale production of recombinant adeno-associated viruses (rAAV) for clinical use involves bioreactors and complex purification processes. Monitoring genomic DNA during manufacturing procedures is crucial to ensure the quality of the final product, as production can vary from batch to batch. We conducted a 50-L bioreactor production, with sampling conducted at each processing step, from transfection to anion-exchange chromatography purification. The rAAV genome can be monitored in transfected cells via a concise DNA extraction method, even in the presence of cellular impurities, using automated electrophoretic quantification with a TapeStation. The rAAV genomic DNA recovery rate was 64% for the affinity column and 41% for anion exchange, as measured using the TapeStation, whereas droplet digital polymerase chain reaction yielded recovery rates of 51% and 45% for the affinity and anion-exchange columns, respectively. Therefore, automated electrophoresis is a reliable and quantitative method for monitoring rAAV genome integrity during production.

REVIEW
  • Tejaswini KAGITA, Seetharam GUDE, Sravan Kumar ABBURI, Ashok DEVARAKON ...
    2025Volume 7Issue 2 Pages 63-81
    Published: 2025
    Released on J-STAGE: August 20, 2025
    Advance online publication: May 08, 2025
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    Three-dimensional (3D) printing is a transformative technology that enables dose individualization in pediatric medicine and advances precision medicine. This facilitates the production of personalized drug formulations with variable dosages, sizes, and release profiles, thereby overcoming the limitations of conventional manufacturing. However, ensuring safety and efficacy requires optimization of critical quality attributes, robust analytical methods, and compliance with good manufacturing practices (GMPs). The PolyPrint consortium is developing innovative polymers and a GMP-compliant fused deposition modeling (FDM) 3D printer. This review covers the formulation strategies, quality considerations, and process validation of 3D-printed pediatric medicines, emphasizing regulatory compliance, printability, and engineering approaches for quality assurance in pharmaceutical applications.

  • Kotoha INOUE, Shinya TAKENOUCHI, Takahisa MURATA
    2025Volume 7Issue 2 Pages 82-85
    Published: 2025
    Released on J-STAGE: August 20, 2025
    Advance online publication: May 29, 2025
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    In allergic inflammation (type I hypersensitivity), the antigen-antibody reaction triggers mast cell degranulation. Inflammatory mediators released by activated mast cells induce vascular hyperpermeability, leading to pronounced inflammation. Understanding these mechanisms is essential for developing novel therapeutic strategies. Vascular permeability is primarily regulated by blood flow and endothelial barrier function. In this review, we summarize how mediators such as histamine, platelet-activating factor, bradykinin, prostaglandin D2, and tumor necrosis factor-α modulate vascular permeability, with a focus on their effects on blood flow and endothelial barrier function in allergic inflammation.

  • Daiki HIRATSUKA, Shizu AIKAWA, Yasushi HIROTA
    2025Volume 7Issue 2 Pages 86-93
    Published: 2025
    Released on J-STAGE: August 20, 2025
    Advance online publication: July 01, 2025
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    Approximately 17.5% of couples worldwide are affected by infertility. Recurrent implantation failure (RIF) affects approximately 20% of patients with infertility undergoing assisted reproductive technology (ART). Although embryonic factors have been addressed using pre-implantation genetic testing, uterine factors remain poorly understood. This review discusses our recent findings on the key molecular factors essential for uterine receptivity and embryo implantation, emphasizing the findings from genetically modified mouse models. Embryonic implantation involves three precisely regulated phases: apposition, attachment, and invasion. In this review, we focus on cyclooxygenase (COX)-mediated prostaglandin (PG) signaling and the Forkhead Box A2 (FOXA2)-LIF-STAT3 signaling axis. COX enzymes, particularly COX-2, regulate decidualization and embryo invasion via PG synthesis. FOXA2-induced leukemia inhibitory factor (LIF) expression in uterine glands is essential for initiating embryo attachment and subsequent stromal LIF expression, thereby contributing to implantation chamber formation. LIF activates epithelial STAT3 signaling and facilitates morphological transformations crucial for implantation. Further understanding of these signaling pathways may yield insights into the mechanisms of implantation, potentially guiding the development of novel therapeutic strategies for RIF.

  • Eri OGURO-IGASHIRA, Kiyoshi TAKEDA
    2025Volume 7Issue 2 Pages 94-102
    Published: 2025
    Released on J-STAGE: August 20, 2025
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    Intestinal metabolites produced by gut microbiota have an important function as signaling molecules for host intestinal immune cells and mediate their effects via G protein-coupled receptors (GPCRs). Recently, an increasing number of novel gut microbial metabolite–GPCR axes have been identified, revealing dynamic and intricate interactions between the microbiota, their metabolites, and the host immune system. These discoveries have highlighted the importance of metabolic communication in regulating intestinal immune homeostasis and the development of various inflammatory and infectious diseases. At the same time, significant advances have been made in developing sophisticated human in vitro models, including organoid and co-culture systems, which have enabled the more precise elucidation of these axes and their underlying mechanisms, overcoming previous technical limitations associated with animal models or traditional cell lines. In this review, we focus on the pyruvate–GPR31 axis, which we have characterized as a key mechanism for maintaining intestinal homeostasis, and provide an overview of immune responses mediated by gut microbial metabolite–GPCR signaling. We also highlight recent progress in the development of innovative co-culture models—particularly those utilizing human cells—that have proven valuable in dissecting the functional impact of gut microbial metabolites on the human immune system.

OVERVIEW
  • Ashok DEVARAKONDA, Seetharam GUDE, Sravan Kumar ABBURI, Sravya MADDINE ...
    2025Volume 7Issue 2 Pages 103-111
    Published: 2025
    Released on J-STAGE: August 20, 2025
    Advance online publication: July 11, 2025
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    The effective oral administration of insulin has the potential to transform diabetes management by improving the quality of life for patients who depend on frequent insulin injections. However, oral insulin delivery faces significant obstacles, including degradation by gastrointestinal enzymes, variable pH environments, and physical barriers such as the mucus and epithelial layers, which result in oral bioavailability as low as ≤2%. To address these challenges, numerous strategies have been explored, with polymeric nanoparticles (PNPs) emerging as a promising approach for enhancing insulin bioavailability via oral routes. This review focuses on the applications of PNPs in oral insulin delivery, emphasizing their potential for overcoming physiological barriers and ensuring controlled and sustained insulin release. It highlights the mechanisms through which PNPs facilitate insulin protection, transport, and release in the gastrointestinal tract, as well as their ability to target specific absorption sites. The review also discusses recent advancements in the design and functionalization of PNPs, such as surface modifications, stimuli-responsive properties, and incorporation of absorption enhancers to improve bioavailability and therapeutic outcomes. Despite promising progress, challenges such as large-scale production, stability during storage, and variability in patient response remain. Furthermore, regulatory and safety considerations must be addressed to accelerate clinical translation. This review serves as a comprehensive guide for researchers aiming to develop advanced PNP-based oral insulin delivery systems. By bridging existing knowledge gaps, it provides a foundation for future innovations that could revolutionize the treatment paradigm for diabetes.

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