In pediatric pharmacotherapy, parents often play a central role in medication management and administration support, and continuous support from community pharmacists is important. However, it remains unclear how continuity of pharmacy use is associated with parent-reported evaluations of pharmacists. This study conducted a web-based survey of 1,788 parents of children younger than 6 years and examined the association between these factors. Parent-reported evaluations of pharmacists were assessed using items adapted based on the Japanese version of the Medical Interview Satisfaction Scale (MISS-21J), with Distress relief, Communication comfort, and Rapport used as evaluation indicators. Multiple linear regression analyses showed that, compared with the usually same pharmacy group, the always same pharmacy group had significantly higher Distress relief and Rapport scores and a significantly lower Communication comfort score. The different pharmacy each time group had a significantly lower Distress relief score than the usually same pharmacy group, whereas no significant differences were observed for Communication comfort or Rapport. These findings suggest that consistent use of the same pharmacy may be associated with parents’ perceived distress relief and rapport with pharmacists. However, the observed differences were small, and their practical and clinical relevance remains uncertain. Further studies are needed to confirm these findings using validated measures and medication-related or clinical outcomes.

Oral administration of aqueous extracts of myoga (Zingiber mioga) alleviates fatty liver disease by decreasing liver weight and hepatic lipogenic gene expression in high-fat diet-fed mice. In the present study, we investigated whether aqueous myoga extract affects biomarkers of metabolic dysfunction-associated steatotic liver disease (MASLD) and insulin resistance-inducing hepatokines in human hepatocytes with MASLD features derived from humanized murine livers in vitro. The results showed that myoga extract decreased intracellular triglyceride content, leading to a reduction in leucine-rich α2 glycoprotein, an MASLD progression marker. Furthermore, myoga extract favorably modulated the secretion of hepatokines, suppressing insulin resistance-promoting hepatokines such as selenoprotein P, while enhancing the secretion of the beneficial hepatokine fibroblast growth factor 21. These findings demonstrated that the myoga extract restores hepatokine balance in MASLD-like hepatocytes in the PXB-cells LA model and facilitated the practical application of this regional specialty in advanced functional foods for the management of MASLD and related metabolic disorders.

Volatile organic compounds (VOCs) in indoor air are emitted from a wide variety of consumer products and building materials and are routinely inhaled through daily activities. Owing to their effects on human health, identifying VOCs from emission sources associated with indoor air pollution is important for effective exposure management. In particular, VOCs from time-varying emission sources, such as daily activities including cleaning, cooking, and eating, often exhibit complex patterns and require sophisticated methodologies for accurate source identification. This study applied sequential air sampling combined with multivariate analysis to identify VOCs from gradual emission sources, one of the time-varying types, in a workplace. Non-targeted analytical data from sequential indoor air samples were analyzed using principal component analysis (PCA) to visualize indoor air quality patterns. The samples were grouped into three clusters: Group I was characterized by decamethylcyclopentasiloxane (D5), possibly associated with the application of personal care products during the hours when people were present in or near the room; Group II was characterized by toluene, ethyl acetate, and trichloroethylene; Group III was located near the center of the PCA score plot. Notably, individual VOCs found by our method were major components of the temporal changes in total VOC observed during multi-day sampling. This approach can be useful for identifying VOCs from gradual emission sources, particularly those related to occupant activities and product use.

Triptans are recommended for early use in the treatment of migraine attacks; however, real-world medication-taking behaviors and their relationship with interictal burden remain insufficiently understood. This study investigated the association between triptan use patterns and interictal burden in patients with migraine. A web-based cross-sectional survey was conducted among 302 women aged 20–59 years with migraine. Interictal burden was assessed using the Migraine Interictal Burden Scale (MIBS-4), and participants were classified into high- and low-burden groups. Triptan use, including frequency, timing of administration during migraine attacks, and patterns of medication use, was evaluated. Triptan use days were lower than headache days in both groups, suggesting that triptans were not used for all headache episodes. No significant differences were observed between groups in the type of triptan used or the timing of administration. In contrast, medication-taking behaviors differed significantly between groups. The high-burden group more frequently exhibited underuse behaviors, such as delaying or avoiding medication, as well as overuse behaviors, including early or additional dosing driven by anxiety. Satisfaction with triptan treatment was higher in the low-burden group, whereas the use of preventive medications did not differ between groups. Multivariable logistic regression analysis identified the coexistence of underuse- and overuse-related behaviors and HIT-6 score as independent factors associated with high interictal burden. These findings suggest that medication-taking behaviors characterized by both underuse- and overuse-related tendencies are independently associated with interictal burden in migraine. Future studies should evaluate whether interventions targeting maladaptive medication-taking behaviors are associated with improvements in headache management and disease burden.

Objective: To describe amitriptyline treatment modifications during a supply-restriction period and evaluate changes in pain intensity in an exploratory analysis. Methods: This single-center retrospective study included adults prescribed amitriptyline for pain management between January and December 2022 who remained on treatment when prescribing restrictions began in April 2023. Discontinuation or switching was assessed through March 2024. The primary endpoint was the proportion of patients who discontinued amitriptyline or switched to another drug for any reason. Treatment modifications were classified as either documented shortage-related or attributable to other clinical reasons. Numerical Rating Scale (NRS) changes were explored among shortage-related cases with paired baseline and 8-week assessments. Results: Of 180 patients screened, 83 were included. During the observation period, 81 patients (97.6%) underwent treatment modification for any reason, and 52 of 83 (62.7%) had treatment modifications explicitly documented as shortage-related. The remaining 29 modifications were attributed to inadequate pain control and/or adverse events. Among the 52 shortage-related cases, paired NRS scores were available for 33 patients. Median NRS scores were 5 [interquartile range (IQR), 3–7] at baseline and 5 [IQR, 4–6] at 8 weeks, with no significant overall change (p = 0.21). Changes did not differ significantly between the discontinuation and switching groups (p = 0.48). All patients with paired NRS scores were treated in the Department of Anesthesiology. Conclusions: Documented shortage-related treatment modification occurred in approximately two-thirds of eligible patients. The NRS findings were exploratory and should be interpreted cautiously because of potential selection bias.

BACKGROUND: Acute kidney injury (AKI) is associated with progression to chronic kidney disease, initiation of dialysis, and a decline in quality of life. Although rising temperatures have been linked to an increased risk of AKI, evidence regarding this association among outpatients in Japan remains limited. This study evaluated the association between community-acquired AKI (CA-AKI) and temperature using prefecture-level aggregated data. METHODS: We used Health Weather, a database integrating Japanese claims data with meteorological information. Among 4,868,549 individuals, we calculated the daily incidence of CA-AKI across 47 prefectures from 2018 to 2019. Associations were evaluated using the Cochran–Armitage trend test. RESULTS: CA-AKI incidence significantly increased as daily mean temperatures rose (p = 0.003). CONCLUSIONS: CA-AKI in Japan is significantly associated with higher temperatures. Preventive strategies should be tailored to the climatic characteristics of each geographic area.

Mesenchymal stromal cell transplantation therapy has been widely studied in regenerative medicine for the treatment of various diseases. We previously developed a mitochondria-targeted drug delivery system, termed the MITO-Porter, which enables large-scale production of coenzyme Q₁₀ (CoQ₁₀)-encapsulated carriers. This study aimed to generate mitochondrial-activated amnion-derived mesenchymal stromal cells (AMSCs) by delivering CoQ₁₀ to mitochondria using the MITO-Porter system, with the potential to improve AMSC transplantation outcomes. We treated AMSCs with CoQ₁₀-encapsulated MITO-Porter and evaluated cellular uptake, co-localization with mitochondria, changes in mitochondrial respiratory capacity, and antioxidant capacity. CoQ₁₀-encapsulated MITO-Porter was internalized by AMSCs and co-localized with mitochondria. Treatment of AMSCs with CoQ₁₀-encapsulated MITO-Porter significantly increased the mitochondrial oxygen consumption rate and decreased superoxide levels. Mitochondrial delivery of CoQ₁₀ successfully enhanced the mitochondrial respiratory capacity and antioxidant ability of AMSCs. These mitochondrial-activated AMSCs, newly generated using the MITO-Porter system, represent a promising cell source for improving MSC-based transplantation therapy.

Zolpidem is a non-benzodiazepine hypnotic that acts on γ-aminobutyric acid (GABA) type A (GABA_A) receptors and is widely used to treat insomnia. Our previous studies demonstrated that inflammation induced by bacterial mimetics, such as lipopolysaccharide (LPS), prolongs zolpidem-induced loss of righting reflex (LORR) in mice, suggesting that systemic inflammatory states modulate GABAergic transmission. However, it remains unclear whether viral inflammation produces similar effects. In this study, we investigated the effect of polyinosinic:polycytidylic acid (poly(I:C)), a synthetic analog of viral double-stranded RNA, on the duration of zolpidem-induced LORR in mice. Poly(I:C) administration significantly prolonged zolpidem-induced LORR. However, this prolongation was attenuated by pretreatment with bicuculline, a GABA_A receptor antagonist, and by bumetanide, an inhibitor of Na⁺-K⁺-2Cl⁻ cotransporter isoform 1 (NKCC1). In addition, we examined the mRNA expression levels of GABA_A receptor subunits, NKCC1, and K⁺-Cl⁻ cotransporter isoform 2 (KCC2) in the hippocampi of poly(I:C)-treated mice. Poly(I:C) treatment did not significantly alter the mRNA expression of major GABA_A receptor subunits but increased Slc12a2 mRNA expression, which encodes NKCC1 in the hippocampus. Importantly, poly(I:C)-induced prolongation of LORR was attenuated by bumetanide, an NKCC1 inhibitor. In conclusion, these findings suggest that viral mimetic-induced inflammation prolongs zolpidem-induced LORR, possibly through alterations in intracellular chloride homeostasis.

Background: Pivalate-conjugated β-lactam antibiotics (PCAs) have been developed to enhance bioavailability by incorporating the pivoxil group into the β-lactam chemical structure. Although there are only case reports and observational studies limited to pediatric patients on PCA-associated hypocarnitinemia, no comparisons have been made across all age groups, and comprehensive data from larger-scale studies are limited. Therefore, we investigated the association between PCA use and the onset of hypocarnitinemia for all age groups by analyzing the Japanese Adverse Drug Event Report (JADER) database. Methods: We analyzed 2,226,010 adverse event cases from the JADER database between April 2004 and March 2024. To detect signals of hypocarnitinemia, we calculated the reporting odds ratio and 95% confidence interval. Results: Among the total reported cases of hypocarnitinemia, the highest number of occurrences (252 cases) and the signal of hypocarnitinemia were detected in PCAs, whereas no cases were observed for other β-lactam antibiotics (non-PCAs). Multiple logistic regression analysis revealed that the PCA use, age (< 10 years), and concomitant use of valproate were associated with the onset of hypocarnitinemia. Most patients with hypocarnitinemia were under 10 years of age. An evaluation based on consumption data analysis from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open database suggested that antimicrobial consumption is highest among children under 10 years of age. Conclusions: Our findings suggest that the use of β-lactam antibiotics containing a pivoxil moiety is disproportionately associated with reports of hypocarnitinemia in the JADER database. These findings should be interpreted as hypothesis-generating.

The coronavirus disease 2019 (COVID-19) pandemic substantially altered the epidemiology of seasonal influenza and markedly reduced the utilization of anti-influenza agents. Although influenza activity resumed following the relaxation of public health interventions, it remains unclear whether the utilization patterns of anti-influenza agents returned to the pre-pandemic state or changed after the pandemic. Prescription volumes of anti-influenza agents were extracted from the National Database of Health Insurance Claims and Specific Health Checkups Open Data (NDB Open Data) for fiscal years (FY) 2019–2024. Oseltamivir, baloxavir, zanamivir, and laninamivir were evaluated. To compare temporal changes among antiviral agents, prescription volumes were normalized using FY2019 as the reference (index = 100). Utilization of all evaluated anti-influenza agents declined markedly during FY2020 and FY2021. However, the recovery patterns differed substantially among antiviral agents following the resumption of influenza activity. In FY2024, the prescription index reached 297.0 for baloxavir 20-mg tablets and 191.6 for oseltamivir capsules/tablets, whereas zanamivir remained at 57.2. Laninamivir recovered to nearly the pre-pandemic level. These findings indicate that post-pandemic drug utilization differed substantially among antiviral agents. In conclusion, utilization patterns of anti-influenza agents in Japan changed following the COVID-19 pandemic. The heterogeneous recovery observed among antiviral agents suggests that post-pandemic utilization patterns may have been influenced by drug-specific characteristics in addition to the resurgence of influenza activity.

Fiber-rich foods are commonly consumed as part of dietary management or self-care by patients receiving long-term cardiometabolic pharmacotherapy. However, their physicochemical interactions with marketed pharmaceutical products under simulated intestinal conditions remain insufficiently characterized. This study evaluated the in vitro adsorption behavior of selected orally administered cardiometabolic drugs in artificial intestinal fluid in the presence of basil seeds or wheat bran. Commercially available products containing calcium channel blockers, beta-blockers, statins, or angiotensin II receptor blocker-related drugs were crushed and dispersed in artificial intestinal fluid, followed by the addition of basil seeds or wheat bran. Residual drug concentrations were determined by HPLC, and adsorption profiles were analyzed using pseudo-first-order and pseudo-second-order kinetic models. The reduction in residual drug concentration depended on both the drug and the food material. In the presence of wheat bran, amlodipine and carvedilol showed marked decreases in residual concentration, with residual rates of 32.9% and 16.6%, respectively, after 3 h. Nifedipine and olmesartan medoxomil also showed decreased residual concentrations, whereas bisoprolol, rosuvastatin, atorvastatin, and azilsartan showed only limited changes. The pseudo-second-order model showed better overall agreement with the adsorption profiles of the selected drugs. These findings provide a basis for further biopharmaceutical evaluation of physicochemical interactions between fiber-rich food materials and orally administered cardiometabolic drugs.

Cyanidin-3-glucoside (C3G) is a major anthocyanin present in various berries and pigmented grains and has been reported to exhibit antioxidant and anti-inflammatory activities. In the present study, we examined the effects of C3G on inflammatory responses in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with particular attention to adipocyte protein 2 (aP2), a lipid-associated protein implicated in inflammation. Treatment with C3G at concentrations up to 50 μM did not affect cell viability in the presence or absence of LPS. Quantitative real-time PCR analysis demonstrated that C3G significantly suppressed LPS-induced expression of aP2, as well as the pro-inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). Furthermore, luciferase reporter assays revealed that C3G inhibited LPS-induced aP2 promoter activity in a manner independent of the peroxisome proliferator-activated receptor response element (PPRE)-like site. These findings indicate that C3G attenuates macrophage inflammatory responses through the suppression of aP2 expression and pro-inflammatory cytokine production, suggesting a novel molecular basis for the anti-inflammatory action of C3G.

This study aimed to identify factors influencing medical consultation among patients with migraine and to explore pharmacists’ roles in promoting appropriate care through the use of pharmacist-provided patient referral forms and burden assessment tools. An internet-based survey was conducted among 400 women aged 20–59 years identified as having migraine using a screening tool. Respondents were classified into the doctor-visited group (those who had visited a medical institution at least once) and the non-doctor-visited group (those who had never visited a medical institution). The doctor-visited group showed significantly higher scores on headache-related burden measures, including the Headache Impact Test-6 (HIT-6) and the Migraine Interictal Burden Scale-4 (MIBS-4) (p < 0.05), and a higher prevalence of symptoms such as aura, photophobia, and osmophobia. Although some participants in the non-doctor-visited group had high HIT-6 and MIBS-4 scores, they tended to perceive their headaches as “mild” or “temporary,” suggesting an underestimation of their burden. Approximately 70% of participants in both groups expressed positive attitudes toward patient referral forms, indicating potential usefulness in reducing anxiety regarding medical consultation. Among respondents in the non-doctor-visited group with little interest in patient referral forms, approximately 80% used over-the-counter (OTC) medications, and some had high HIT-6 and MIBS-4 scores. These findings suggest the potential role of burden assessment tools and patient referral forms in supporting patients in considering appropriate medical consultation during pharmacist intervention at the time of OTC medication purchase.

Distinguishing between disease-induced and drug-associated hyponatremia is important in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. This study aimed to characterize the specific reporting profile of linezolid (LZD)-associated hyponatremia using the Japanese Adverse Drug Event Report (JADER) database. Data from the JADER database (April 2004‒May 2025) were analyzed. Crude reporting odds ratios (cRORs) for hyponatremia were calculated to confirm the safety signal for LZD. Subsequently, multivariate logistic regression and Weibull distribution analyses were performed for LZD-associated cases to explore demographic factors associated with the reporting and temporal reporting profiles, respectively. Among 4,480 reports of hyponatremia, 117 were associated with anti-MRSA agents (LZD, tedizolid, vancomycin, teicoplanin, daptomycin, and arbekacin). LZD demonstrated a significant reporting signal for hyponatremia (cROR, 10.04; 95% confidence interval [CI], 8.19–12.31). This signal persisted even in the oral administration subgroup (cROR, 3.41; 95% CI, 1.83–6.38). The multivariate logistic regression analysis restricted to LZD-associated cases identified age ≥ 70 years (adjusted reporting odds ratio [aROR], 1.73; p < 0.001) and female sex (aROR, 1.52; p < 0.05) as demographic factors associated with the reporting. The median time to onset was 5.5 days. The Weibull shape parameter (β) was 1.34, indicating an increasing reporting hazard profile over time during the acute treatment period. These hypothesis-generating findings suggest that cumulative exposure to LZD may lead to hyponatremia, supporting the need for careful serum sodium monitoring, particularly in elderly and female patients.

Environmental contamination from antineoplastic drugs poses a significant occupational health risk to healthcare professionals. Herein, we evaluated the efficacy of a recently developed decontamination method using hypochlorous acid (HClO) water and alkaline electrolyzed water (AEW) compared to conventional cleaning, focusing on the physicochemical properties of target drugs. Decontamination efficacy was assessed on work desks and clean benches using an ATP bioluminescence assay (RLU values). Additionally, a wipe test was conducted on stainless-steel plates contaminated with 5-fluorouracil (5-FU), gemcitabine (GEM), and paclitaxel (PTX) to quantify residual drug concentrations after cleaning with either distilled water/ethanol or HClO/AEW. Cleaning with HClO and AEW significantly reduced the RLU values compared to those from conventional cleaning (distilled water and ethanol) (p < 0.05), achieving levels below the standard threshold of 200 RLU. Regarding the wipe test, HClO and AEW demonstrated superior removal efficacy for the hydrophilic drugs 5-FU and GEM (p < 0.05). Conversely, residual levels of the highly lipophilic drug PTX (log P = 2.5) were significantly higher following HClO/AEW cleaning than those from the ethanol-based method. The combination of HClO and AEW provides excellent baseline cleanliness and is highly effective for decontaminating surfaces with hydrophilic antineoplastic drugs. However, its efficacy in removing lipophilic agents, such as PTX which may form hydrophobic films, is limited. These findings suggest that a multilayered decontamination strategy, such as HClO treatment with an ethanol wipe, is essential for comprehensive safety, and provide a scientific basis for selecting cleaning protocols based on the log P-values of handled hazardous drugs.

Liposomes have been widely utilized as drug carriers to achieve the efficient tumor accumulation of anticancer drugs through the enhanced permeability and retention effect. However, due to their rigid lipid membranes, drug release from liposomes is limited in tumor tissues, thereby compromising anti-tumor efficacy. Therefore, the development of technologies that selectively promote drug release from liposomes in tumors is required. We previously demonstrated that polyethylene glycol (PEG)-modified sorbitan monooleate (Span 80) niosomes (PEG-Span 80 niosomes) enabled the triggered release of doxorubicin from the aqueous core of PEG-modified liposomes (PEG-liposomes). In the present study, we investigated whether PEG-Span 80 niosomes also promote the release of paclitaxel (PTX) from the lipid bilayer of PEG-liposomes. In addition, the triggering effect of PEG-modified sorbitan trioleate (Span 85) niosomes (PEG-Span 85 niosomes) on PTX release from PEG-liposomes was evaluated. PTX release from PEG-liposomes was significantly enhanced from early time points in the presence of PEG-Span 80 niosomes, and the amount released at 48 h was approximately 3.9-fold larger than that in the absence of PEG-Span 80 niosomes. Moreover, PEG-Span 85 niosomes promoted PTX release from PEG-liposomes, and the amount of PTX released in the presence of PEG-Span 85 niosomes was approximately 2.1-fold larger than that in the presence of PEG-Span 80 niosomes. In addition, the triggered release of PTX from PEG-liposomes induced by PEG-Span 85 niosomes was partially attributable to membrane fusion between these particles. These results provide valuable information for the realization of safe and effective liposome-based cancer chemotherapy.

Bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor and inhibits angiogenesis, can cause hypertension. Although blood pressure generally rises in winter and falls in summer, seasonal patterns of bevacizumab-related hypertension (BRHT) remain unclear. We investigated these patterns using Japanese Adverse Drug Event Report data from July 2007 to June 2025. Cases where bevacizumab was reported as a “suspected drug” were identified using the Medical Dictionary for Regulatory Activities preferred terms “hypertension,” “blood pressure increased,” or “systolic blood pressure increased.” Monthly relative BRHT frequencies were calculated by dividing BRHT reports by the total adverse event reports and compared with mean monthly temperatures obtained from the Japan Meteorological Agency. Seasons were defined as spring (March–May), summer (June–August), autumn (September–November), and winter (December–February), and were visualized using mosaic plots. Between April 2004 and September 2025, 985,999 reports were registered, of which 956 met the BRHT criteria. The median time-to-onset (TTO) was 21.0 days (interquartile range, 7.0–45.0). The Weibull scale parameter (α) was 40.8 (95% confidence interval [CI]: 37.4–44.5), and the shape parameter (β) was 1.06 (95% CI: 0.99–1.13). BRHT reports peaked in September and October and were least frequent in summer. No significant differences were observed in either TTO or clinical outcomes across seasons of adverse event onset. BRHT occurred more frequently in autumn, particularly in September and October, than in winter. Healthcare professionals should be aware of this seasonal risk and ensure appropriate blood pressure monitoring and preventive measures during autumn.

Progression of metabolic dysfunction-associated steatotic liver disease leads to insulin resistance, a condition driven by the induction of specific hepatokines. We previously developed an in vitro steatotic liver model, PXB-cells LA (Lipid Analysis), derived from fresh human hepatocytes (PXB-cells^®) isolated from humanized mouse livers. In the present study, we investigated its utility as a screening system for insulin-sensitizing agents. Our results demonstrated that metformin and rosiglitazone, well-known treatments for type 2 diabetes, reduced the expression of the prodiabetic hepatokines leukocyte cell-derived chemotaxin 2 and fetuin-A in PXB-cells LA. Furthermore, while fibroblast growth factor 21 enhances systemic insulin sensitivity, both agents upregulated fibroblast growth factor 21 production at both the mRNA and protein levels in this model.

Insomnia is highly prevalent among older adults, and hypnotics are widely prescribed in Japan. As older individuals are vulnerable to hypnotic-related adverse events, such as falls and cognitive impairment, monitoring national prescription trends is essential for safer pharmacotherapy. Using the National Database Open Data from fiscal years 2019–2023, we examined nationwide prescription trends of hypnotics indicated for insomnia (or insomnia with pre-anesthetic medication). We calculated the annual total dispensed quantity, the dispensed quantity attributable to adults aged ≥65 years, and the proportion (%) of dispensed quantity among older adults. Conventional hypnotics (benzodiazepines and Z-drugs) and newer agents, including dual orexin receptor antagonists (DORAs), were evaluated. Zolpidem remained the most frequently used hypnotic, increasing from 506 million dispensed dosage units in 2019 to 685 million in 2023. However, the proportion of dispensed quantity attributable to adults aged ≥65 years declined from 64.7% to 60.2%. Brotizolam exhibited a similar utilization trend, with stable overall use but a reduction from 66.6% to 62.1% in the older adult population. In contrast, lemborexant, introduced in 2020, demonstrated a rapid uptake, reaching 504 million dispensed dosage units in 2023, whereas its proportion of use among older adults increased from 38.9% to 51.1%. Insomnia medication prescription trends are shifting in Japan, with the increasing adoption of DORAs along with a relative decline in conventional hypnotics among older adults. Continued monitoring is warranted to support safer prescription practices in geriatric insomnia care.

High mobility group box 1 (HMGB1) is a critical pro-inflammatory damage-associated molecular pattern (DAMP), and ribosomal protein L9 (RPL9) has been identified as a potential “regulatory DAMP” that can suppress HMGB1’s activity. However, it is unclear how pro-inflammatory DAMP signaling is initiated when these opposing molecules are released together. We hypothesized that the release kinetics of HMGB1 and RPL9 are differentially regulated depending on the cell type. To test this, we compared the release of HMGB1 and RPL9 from human macrophage (THP-1), liver (HepG2), and endothelial (EA.hy926) cell lines following stimulation with lipopolysaccharide and nigericin. In THP-1 macrophages, classical pyroptosis induced a rapid, sequential release of HMGB1 followed by RPL9. In contrast, HepG2 cells showed slower, apoptosis-like cell death, and RPL9 was released several hours before HMGB1. EA.hy926 cells were highly resistant to the stimulus. Notably, RPL9 release was closely associated with phosphatidylserine externalization in both THP-1 and HepG2 cells, regardless of their primary cell death pathway. Our findings demonstrate that the balance between pro-inflammatory and regulatory DAMPs is governed by a complex, cell-type-specific temporal control system intrinsically linked to the mode of cell death. Furthermore, we propose the existence of a novel, selective release pathway for RPL9. A deeper understanding of this time-dependent regulation may contribute to the development of new therapeutic strategies for inflammatory diseases.

Mitochondria play essential roles in cellular redox homeostasis and viability, and oxidative stress is known to impair mitochondrial function. In this study, we examined the effects of pyridoxine hydrochloride (vitamin B₆) on mitochondrial responses in normal human dermal fibroblasts (NHDFs) exposed to hydrogen peroxide (H₂O₂). Pre-treatment with pyridoxine hydrochloride was associated with changes in mitochondrial responses, including increased cell viability, higher PCR-based mtDNA amplifiability (an indirect indicator of mtDNA integrity), and maintenance of mitochondrial membrane potential under oxidative stress conditions. These observations indicate that pyridoxine hydrochloride influences mitochondrial responses to oxidative stress in this in vitro model, and suggest its utility for evaluating small-molecule antioxidants.

Objective: In October 2024, the Selected Medical Care System, a patient cost-sharing scheme for off-patent brand-name drugs, was introduced to promote the use of generic drugs (GEs). To clarify the impact of introducing this system on the rate of GE usage, we examined the degree of change following its implementation. Methods: We analyzed the volume share of GEs (September 2019 to March 2025) using an interrupted time-series design with a linear mixed model, and assessed the deviations of individual insurers from historical trends by calculating 95% prediction intervals using linear regression. Results: The median GE volume share of all 1,877 organizations increased from 0.854 in September 2024, immediately prior to introduction of the Selected Medical Care System, to 0.902 in March 2025, revealing that the median half-year-on-half-year rate of change increased from +0.021 to +0.057. Linear mixed modeling confirmed the positive impact of the system on GE volume share among professional subgroups, even after controlling for pre-existing trends, whereas trend analysis revealed that 92.4% (146/158) of the analyzed organizations showed deviations from their historical trends during the post-implementation period. Conclusions: The system for selected medical care coverage has had a notable effect regarding the promotion of GE use and can be considered an effective measure for encouraging behavioral change, even in groups for which the rate of GE usage is generally relatively low.

Objective: There is increasing research interest on the impact of ischemic stroke on organs beyond the central nervous system, and it is now widely recognized that cerebral ischemia induces multiple alterations in peripheral systems. Therefore, it is necessary to elucidate the systemic consequences of cerebral ischemia. Serine protease inhibitor a3 (SERPINA3), a secretory immune-related molecule produced primarily in the liver and brain under normal conditions, is upregulated in response to inflammation. Here, we examined Serpina3n gene expression in the brain and liver and evaluated plasma SERPINA3N protein concentrations following cerebral ischemia using a mouse model. Methods: We examined changes in SERPINA3N levels in the brain, liver, and blood over time using a mouse model of focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion for 4 h followed by reperfusion. Brain, liver, and blood samples were collected on days 1, 3, and 7 after MCA occlusion (MCAo). Serpina3n gene expression levels in the brain and liver were measured by quantitative real-time polymerase chain reaction (qPCR), and plasma SERPINA3N levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Serpina3n gene expression levels in the brain and liver were increased on day 1 after MCAo. Plasma SERPINA3N protein levels were increased and peaked on day 1 after MCAo. Conclusion: A mouse model of cerebral ischemia showed increased Serpina3n gene expression in the liver and SERPINA3N protein level in plasma. This is the first study of the effects of plasma SERPINA3N protein levels using a mouse model of cerebral ischemia.

Moderate midazolam sedation is often used in gastrointestinal endoscopy to induce stress-free conscious sedation. Conversely, flumazenil can reverse midazolam-induced sedation and cause temporary awakening and resedation. However, the effects of flumazenil disuse on the incidence of inpatient falls are unknown. In this study, we performed a retrospective cohort analysis of the incidence of falls in inpatients who underwent gastrointestinal endoscopy under midazolam-induced sedation with or without flumazenil. This study included 1,424 procedures, of which 559 involved flumazenil use. The frequency of inpatient falls did not significantly differ between the flumazenil and nonflumazenil use groups (2/559 episodes [0.36%] vs. 2/865 episodes [0.23%], P = 0.648). The inverse probability of treatment weighting analysis could not determine the association of flumazenil disuse with the incidence of inpatient falls (odds ratio, 0.57; 95% confidence interval, 0.08-4.14; P = 0.58). Our results indicate that the association between flumazenil disuse and the incidence of inpatient falls remain unclear.

As part of our ongoing study on verification of helium–alternative carrier gases in the official test method using gas chromatography–mass spectrometry (GC–MS) for chemicals in indoor air, we examined the applicability of hydrogen and nitrogen to thermal desorption (TD)–GC–MS. A comparison of the signal–to–noise ratios of standard solutions of volatile organic compounds (VOC) and Phthalate esters showed that detection sensitivities of hydrogen and nitrogen analyses were sufficient for the official test method. Measurements using these alternative carrier gases showed good linearity and could quantify less than 1/100^th of Japanese guideline values for indoor air concentrations. Therefore, hydrogen and nitrogen gases can be applied to the official test method using TD–GC–MS for VOC and Phthalate esters in indoor air as alternative carrier gases to helium.

Benzotriazole-based ultraviolet absorbers (BUVs) are widely used in polymers due to their high thermal and photo stability. However, their environmental persistence and bioaccumulation potential have raised concerns, and some have become subject to regulation. BUVs have been detected in water, air, road dust, biota, and indoor products such as plastics and paints. They have also been frequently found in household dust (HD), which accumulates semi-volatile organic compounds; however, no studies to date have investigated the presence of BUVs in Japanese HD. This study established an LC–MS/MS method with atmospheric pressure chemical ionization (APCI) to quantify eight BUVs in HD and evaluate their occurrence in Japanese residences. Here, eight BUVs were selected for analysis, including UV-320—classified as a Class I specified chemical substance under Japan’s Chemical Substances Control Law—and UV-328, newly listed in 2024. Sample preparation was optimized by evaluating six solid-phase extraction methods, among which basic alumina-based cartridges demonstrated selective BUV retention. High recoveries ranging from 86.9 to 100% were achieved using a back-flush elution approach. Using the developed method, HD samples collected in 2023 and 2024 were analyzed. Six compounds, excluding UV-320 and UV-PS, were detected in 100% of the samples. Although the maximum and minimum concentrations varied considerably between the two years, the median values and detection frequencies showed generally consistent trends. These findings reveal the contamination status of BUVs in Japanese HD and demonstrate that the developed APCI–LC–MS/MS method is a reliable approach for indoor pollution monitoring.

Telomeric repeat-containing RNA (TERRA), a long non-coding RNA (lncRNA), is transcribed from both chromosomal ends and regulates gene expression at telomeres as well as within internal chromosomal regions. Although chromosomal dysfunction has been implicated in depression, the relationship between TERRA expression and depressive symptoms remains poorly understood. In this study, we developed a quantitative reverse transcription PCR (RT-qPCR) method to measure TERRA expression from 10 loci on chromosomes 3, 8, 11, 12, 16, and 22, which have been associated with depressive disorder. Using this method, we examined the association between TERRA expression in peripheral blood and depressive symptoms in 18 patients with major depressive disorder. TERRA expression levels at 8p and 11p exhibited limited correlation with those at other chromosomal loci. Moreover, when patients were stratified into two groups based on depressive symptom severity, TERRA expression at 8p was significantly lower in the group with severe depressive symptoms compared with those with mild symptoms (P = 0.043). This study established a method for quantifying chromosome-specific TERRA expression and provided insights into its potential association with depressive symptoms. The findings suggest that aberrant TERRA expression at 8p may contribute to the pathophysiology of depression. Further studies involving larger cohorts are warranted to validate these results.