This perspective examines whether animal models can be gradually replaced by human-relevant New Approach Methodologies (NAMs) in drug development and regulatory evaluation, synthesizing recent advances across hepatology, oncology, neurotoxicology, and cardiac safety assessment. Although the relevant technologies have become increasingly mature, their acceptance at the regulatory level is still lagging due to factors such as limited standardization, insufficient reproducibility of results, and unclear approval pathways. Building on a systematic comparison of existing evidence, this article proposes a three-stage transition pathway: the first stage (auxiliary stage)—using NAMs in parallel with animal experiments; the second stage (partial replacement stage)—using NAMs as the preferred efficacy evaluation model for human-specific diseases; and the third stage (regulatory integration stage). Only through gradual validation can animal models be replaced responsibly, thereby increasing the success rate of translational research and reducing the use of animal experiments. Overcoming the persistent challenges of limited standardization, poor reproducibility, and unclear regulatory pathways is the central prerequisite for this transition.

This study aimed to assess the availability of renal function laboratory values in Japanese community pharmacies and examine their association with the prescription of drugs requiring dosage adjustment. In this cross-sectional observational study, data were obtained from the electronic medical records of a community pharmacy in Japan. A total of 389 eligible patients (aged ≥ 18 years) who visited the pharmacy in April 2024 were included. The primary outcome measures were the proportion of participants with available renal function laboratory values and those prescribed medications requiring dosage adjustment. A total of 128 patients (32.9%) were prescribed at least one medication requiring dosage adjustment, most commonly vitamin A and D preparations (32 cases) and antidiabetic agents (31 cases). Renal function laboratory values were available for 40 patients (10.3%). Compared to those not prescribed such drugs, patients receiving medications requiring renal-based dosage adjustments included a significantly higher proportion of older adults (70/128, 54.7% vs 98/261, 37.5%, p = 0.001) and patients with available laboratory values (20/128, 15.6% vs 20/261, 7.7%, p = 0.015). No patients were identified with the "Triple Whammy," which is known to significantly increase the risk of renal function deterioration. Community pharmacists endeavor to obtain renal function laboratory values for older adults, who are more likely to be prescribed medications requiring dosage adjustment. However, the proportion of cases with obtained laboratory values remains low. Pharmacists are expected to actively recommend renal function testing to physicians. Furthermore, they should contribute to safe pharmacotherapy by utilizing comprehensive patient information.

The metabolic and endocrinological effects in patients with adult growth hormone deficiency (AGHD) who switched from daily growth hormone (GH) replacement therapy to weekly GH replacement therapy with somapacitan were evaluated and observed over a long follow-up period. Patients were included only if their medical treatments, aside from GH replacement therapy, remained unchanged. Metabolic and endocrinological parameters were assessed at the time of switching, and at 1- and 2-year follow-up after switching from daily GH replacement therapy to weekly GH replacement therapy with somapacitan. The results showed that the body mass index (BMI), fasting plasma glucose (FPG), aspartate transaminase (AST), and triglyceride (TG) levels at 1 year after switching significantly improved compared with those at the time of switching (each P < 0.025). At 2 years, the homeostasis model assessment of insulin resistance (HOMA-IR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and alanine aminotransferase (ALT), as well as BMI, FPG, TG, and AST significantly improved compared with those observed at the time of switching (each P < 0.025). In addition, improvement in HOMA-IR at 2 years after switching was significantly associated with improvement in AST. Switching to GH replacement therapy did not affect endocrinological parameters. These findings, which were revealed by the present real-world exploratory cohort study, indicate that weekly GH replacement therapy with somapacitan may confer more beneficial effects than daily GH replacement therapy.

The relationship between fear severity and satisfaction after vaginal delivery was examined with a focus on its association with epidural analgesia. Postpartum cross-sectional questionnaire survey was conducted among 201 healthy women after vaginal delivery in Japan. The participants completed the Japanese Wijma Delivery Experience Questionnaire (JW-DEQ) Version B and the short version of the Childbirth Experience Self-Rating Scale, and were grouped by use of epidural analgesia and/or fear severity. Data were analyzed using Spearman correlation, Mann–Whitney U, and chi-square tests. No significant association between fear and satisfaction was found in the women without epidural analgesia. The proportion of women with severe fear of childbirth, defined as a JW-DEQ Version B score ≥ 85, was 39%. In the postpartum-recalled severe fear group, epidural analgesia was associated not only with higher overall satisfaction but also higher scores in its sub-factors: "labor pain coping" and "trust in medical staff". In contrast, epidural analgesia was associated only with "labor pain coping" score in the light fear group. Epidural analgesia induced higher childbirth satisfaction among women with severe fear. Although this study is limited by its cross-sectional design, potential recall bias, and the focus on a specific patient population, which may affect the generalizability of the findings, the factors of "labor pain coping" and "trust in medical staff " seem to be important to avoid fear of childbirth for giving childbirth satisfaction.

The annual periodicity of psychiatric symptoms in older adults within long-term care remains under-explored. This exploratory, single-center, retrospective pilot study investigated seasonality in agitation/aggression, depressive symptoms, and hallucinations/delusions among 28 older Japanese inpatients (mean age 74.1 ± 9.1 years) over a one-year period to inform the chronobiological optimization of pharmacotherapy. Generalized Linear Mixed-effects Models (GLMMs) with trigonometric terms were used to assess periodicity based on daily clinical records. A possible seasonal pattern, with the model-estimated peak in March and nadir in September, was observed for agitation/aggression (Incidence Rate Ratio [IRR] = 1.50, p = 0.037) and depressive symptoms (IRR = 1.08, p = 0.041). Hallucinations/delusions showed no significant periodicity. These findings suggest that older adults in long-term care retain sensitivity to seasonal environmental changes, with spring representing a potential period of circadian vulnerability. These findings may help identify periods requiring closer clinical monitoring and medication review, although prospective studies are needed before seasonally guided dosage adjustments can be recommended.

Ferulic acid (FA) from rice bran is known to possess strong antioxidant properties. Furthermore, its multifunctional properties, such as skin whitening, anti-glycation, and anti-inflammatory effects, have attracted attention. We undertook an exploratory study to examine whether FA might be associated with improvements in skin dullness. A single-blind study was conducted on 24 healthy women, in which a cream containing 1% FA was applied to one side of the face and a placebo cream was applied to the other side to verify the effects. To explore the molecular mechanism, RNA-seq was performed on HEKn keratinocyte and Hs68 fibroblast, followed by qRT-PCR. In the human clinical trial, the melanin index significantly decreased in the area where the FA cream was applied, and a questionnaire also subjectively confirmed the improvement of dark and yellowish dullness by FA cream. RNA-seq analysis of HEKn cells treated with FA revealed significant changes in the expression of FGF-2 (basic fibroblast growth factor) promoting melanocyte proliferation, and CD36 (cluster of differentiation 36), related to the removal of advanced glycation end-products (AGEs). qRT-PCR confirmed that FA significantly downregulated FGF-2 and upregulated CD36 expression. These results suggest that FA may exert its effects by regulating the expression of genes involved in melanogenesis and glycation, contributing to the suppression of melanin production and the reduction of AGEs for the improvement of dull skin.

Population aging is increasing worldwide, accompanied by a rising prevalence of cognitive decline and dementia, imposing substantial healthcare and socioeconomic burdens. This study evaluated the effects of lactoferrin on scopolamine-induced memory impairment in 5-week-old ddY mice using the Barnes maze test and the novel object recognition assay to assess cognitive function. Additionally, gene expression levels in the hippocampus were analyzed using reverse transcription-quantitative PCR to explore the underlying mechanisms. Scopolamine impaired spatial and object recognition memory, whereas lactoferrin markedly improved these deficits, with effects comparable to those of donepezil. Scopolamine also increased inflammatory and oxidative stress markers (Tnf and Nos2) and the apoptosis-related factor (Casp3), all of which were attenuated by lactoferrin. These findings indicate that lactoferrin improved scopolamine-induced memory impairment, potentially by suppressing inflammation and oxidative stress, thereby inhibiting neuronal apoptosis. Therefore, lactoferrin may represent a promising functional food component for the prevention of cognitive decline.

Tyrosine hydroxylase (TH) is the rate‑limiting enzyme in catecholamine biosynthesis, and its activity is regulated by its phosphorylation at specific serine (Ser) residues. In the present study, we investigated the effects of docosahexaenoic acid (DHA) supplementation on TH protein expression and phosphorylation at Ser31 and Ser40 during differentiation in the neuroblastoma–glioma hybrid cell line NG108-15. TH protein expression and phosphorylation levels were analyzed on day 0 (undifferentiated) and on days 5 and 6 (differentiated). Differentiation increased TH protein expression on days 5 and 6, and DHA supplementation did not affect these increases. Phosphorylation at Ser31 showed no significant change with differentiation. By contrast, phosphorylation at Ser40 exhibited a significant increase with increasing days of differentiation, and this was further augmented by DHA treatment. Collectively, these findings suggest that DHA enhances TH phosphorylation, particularly at Ser40, without affecting TH protein expression. DHA may therefore influence brain function not through changes in TH expression levels, but rather through the phosphorylation of TH at Ser40.

This pilot study evaluated whether salivary pregabalin concentrations reflect plasma levels in Japanese volunteers to support non‑invasive therapeutic drug monitoring (TDM). Four healthy adults received a single 75‑mg orally disintegrating tablet; unstimulated saliva and venous blood were collected 1 hour post‑dose using a standardized passive‑drool protocol with pre‑collection rinsing. Pregabalin was quantified by a high-performance liquid chromatography with fluorescence detection. The assay met bioanalytical performance criteria across both matrices (excellent linearity, recovery > 94.2%, precision ≤ 10%, stability within 5.2%). At 1 hour, median concentrations were 1.96 μg/mL (plasma) and 0.466 μg/mL (saliva). In paired analysis (n = 4), saliva and plasma showed a positive trend (r = 0.838, p = 0.298). Given the small sample size, these results are considered exploratory and demonstrate the feasibility of the analytical approach rather than providing definitive clinical evidence. Under standardized collection conditions, salivary pregabalin concentrations appear to yield clinically interpretable estimates of systemic exposure, warranting validation in larger, multi‑time‑point cohorts to establish actionable saliva‑to‑plasma conversion thresholds and evaluate clinical utility.

Dysbiotic wound microbiota, which is dissimilar to that of the peri-wound skin, delays healing in hard-to-heal wounds. However, rapid and practical methods for detecting wound dysbiosis are lacking and the characteristics of the wound environment in which dysbiosis occurs remain unclear. Consequently, microbiota-targeted care to prevent delayed healing has not yet been established. This study investigated the association between amino acid profiles in wound exudates and the degree of microbial dissimilarity between the wound and peri-wound skin microbiota. Nine wounds from eight patients receiving home care were analyzed. The concentrations of 18 amino acids were measured using high-performance liquid chromatography, and the microbiota were detected using 16S rRNA gene amplicon sequencing. The microbial dissimilarity was assessed using the weighted UniFrac dissimilarity index, and correlations between the relative abundances of amino acids, amino acid ratios, and microbial dissimilarities were evaluated using Spearman's rank correlation. Most of the wounds were in the healing phase. The relative abundance of arginine showed a strong correlation with microbial dissimilarity (ρ = – 0.80, p = 0.01). Additionally, eight amino acid ratios (arginine/asparagine and arginine/tyrosine) were significantly correlated with microbial dissimilarity. These findings support the development of point-of-care tools for assessing wound microbiota and improving wound management.