Shibuya (Japan)

Methylmercury (MeHg) is a well-known environmental neurotoxicant that preferentially affects sensory neurons in the peripheral nervous system. While sensory-dominant neuropathy has long been described in Minamata disease, the temporal dynamics of dorsal root ganglion (DRG) injury and recovery remain incompletely understood. In this study, Wistar rats were exposed to MeHg for five consecutive days, followed by a two-day treatment-free period; this regimen was repeated once. The DRG and peripheral sensory fibers were analyzed up to 70 days after exposure. Histological and immunohistochemical analyses, DNA microarrays, and mercury quantification and distribution mapping were performed. The A-fiber density was significantly reduced at Day 14 but recovered by Day 70, whereas C-fibers showed no significant change. The total number of DRG neurons remained stable. Immunohistochemical analyses demonstrated that subtype marker-selected neurons (NF, TrkA, FAM19A1, TAC1, SST) decreased at Day 14 and gradually recovered thereafter. DNA microarray analysis at Day 14 revealed a broad downregulation of DRG neuronal subtype marker genes. The mercury concentration in the DRG peaked at Day 14 and declined to the control level by Day 70, with in situ imaging confirming preferential accumulation in DRG neurons. These data suggest that the short-term MeHg exposure caused a transient functional suppression of DRG neurons without widespread neuronal loss. The selective and reversible downregulation of neuronal phenotypes, coupled with preferential Hg accumulation in DRG neurons, underlies the sensory-dominant and potentially reversible features of MeHg neurotoxicity.

IntroductionRefractory foot ulcers, characterized by prolonged healing and frequent recurrences, challenge existing therapies such as revascularization and compression, which typically fail to prevent amputation. We developed adipose-derived mesenchymal stem cell line-derived platelet-like cells (ASCL-PLCs) for refractory ulcers that are long-lasting and readily available.MethodsA translational preclinical investigation and phase 1/2a first-in-human clinical study assessed the safety and efficacy of a novel allogeneic ASCL-PLC treatment for refractory foot ulcers. In the pre-clinical phase, ASCL-PLCs were cryopreserved for 9 months and then thawed to measure cytokine release after calcium chloride stimulation. The therapeutic efficacy was evaluated in a diabetic mouse wound model, comparing ASCL-PLC treatment with vehicle control. The clinical trial involved topically applying ASCL-PLCs (1.5 × 108 cells/cm2) to the ulcers of four patients (two ischemic, two venous) on days 0, 14, and 28, with safety and efficacy monitored based on adverse events, ulcer size reduction, epithelialization time, and pain score changes.ResultsASCL-PLCs maintained considerable cytokine-releasing activity even after long-term cryopreservation. In the diabetic mouse skin defect model, treatment with ASCL-PLCs substantially enhanced wound closure compared with the controls, demonstrating potent wound-healing capabilities. In the clinical trial, all patients exhibited notable ulcer size reduction without serious adverse events; three achieved epithelialization within 6 months, along with improvements in pain and quality of life without a negative impact on local blood flow.ConclusionsASCL-PLCs are safe and a promising therapeutic option for refractory ulcers and can potentially reduce amputation rates, improve patient outcomes, and minimize the socioeconomic impact due to chronic wounds. Their long shelf life and cryopreservation stability make wound management practical and accessible. Moreover, their efficacy with simple topical application suggests a minimally invasive strategy suitable for outpatient care. Further large-scale trials are recommended.This study was registered with the Japan Registry of Clinical Trials (jRCT ID: jRCTa030200053; on June 18, 2020, https://jrct.mhlw.go.jp/en-latest-detail/jRCTa030200053).

Canine cutaneous epitheliotropic lymphoma (CEL) is a rare neoplastic disease with poor prognosis. Oclacitinib, a Janus kinase inhibitor primarily used to treat allergic and atopic dermatitis in dogs, may also cause other skin diseases. This study aimed to evaluate the efficacy of oclacitinib in the treatment of canine cutaneous lymphoma. Eight client-owned dogs with CEL were included in the study. The dogs were administered oclacitinib. This study examined the immunological characteristics, time to treatment initiation, dosage, cutaneous lesions and pruritus, adverse events, survival time and prior oclacitinib use. Only one of the eight dogs (12.5%) showed symptomatic improvement after oclacitinib treatment, with no clinical improvement observed in the other cases. Improvement in pruritus was noted in only one dog. Adverse events included mild leucopenia in one dog, which did not significantly affect prognosis. The median survival time after diagnosis was 228.5 days. These results suggest that oral oclacitinib has limited efficacy in the treatment of canine CEL. Larger prospective studies are recommended to further investigate the optimal dose, treatment duration and potential combination therapies involving oclacitinib.

Depression is a common mood disorder in systemic lupus erythematosus (SLE) patients, affecting quality of life and medication adherence. Sleep-disordered breathing (SDB) is a known contributor to depression in the general population, but its prevalence and impact on depression in SLE remain unclear. This study aimed to investigate the prevalence of SDB and its association with depression. A cross-sectional study was conducted among 414 Japanese adults with SLE from five university hospitals. The main exposure was high-risk SDB, assessed with the Berlin Questionnaire. The main outcome was moderate to severe depression evaluated using the Patient Health Questionnaire-9. Poisson regression models with robust error variance estimated adjusted prevalence ratios (aPRs). The mean age and body mass index were 47.5years and 22.1kg/m2, respectively. The prevalence of high-risk SDB and moderate to severe depression were 15.2% (95% confidence interval: 11.9-19.0%) and 19.1% (95% CI: 15.4-23.2%). High-risk SDB was associated with moderate to severe depression (aPR 2.63, 95% CI 1.62-4.27), with a dose-dependent relationship according to the number of positive risk categories. SDB is common in SLE and is associated with depression. SLE patients with SDB symptoms should undergo concurrent depression screening.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Single-use plastics (SUPs) are deeply embedded in everyday consumption in rapidly developing Asian cities, yet their widespread use contributes to marine debris, microplastic pollution, and health risks. This study aimed to inform evidence-based policymaking to mitigate marine plastic pollution in the ASEAN+3 region. Stratified random sampling surveys (n = 1492) were conducted both face to face and online across five representative cities between September 2022 and February 2023. We quantified and compared the consumption and disposal patterns across nine SUP categories, assessed demographic influences, evaluated the impact of COVID-19, and derived insights for targeted policy interventions. Non-parametric tests were used to evaluate the differences. The results reveal significant inter-city variation: Shanghai and Harbin reported high overall SUP use despite a lower consumption of plastic shopping bags; Hanoi and Depok showed lower overall use but distinct preferences for plastic shopping bags and party cups; and Phnom Penh had the highest consumption of plastic shopping bags, bottles, and straws. Plastic shopping bags were the most used item in all cities (18–34 bags per week), with no significant differences between urban and rural areas, ages, or genders. In contrast, urban residents reported a higher use of plastic takeout containers, cutlery, coffee cups, and party cups. The COVID-19 pandemic notably reshaped SUP consumption patterns. Additionally, over half of SUPs were disposed of without proper separation. These findings underscore the need for flexible, phased, and context-specific interventions to support a resilient circular economy.