Tsurumi University

Well-known risk factors for soft tissue heterotopic ossification (HO) include aging and mechanical stress, which may be linked to oxidative stress and downstream nucleotide metabolites. Thus, we investigated the involvement of extracellular ATP (ex-ATP) and its metabolites in the oxidative stress-induced mineralization of TT-D6 cells and primary mouse tendon cells. An osteogenic culture with the intermittent addition of hydrogen peroxide was monitored for two weeks using metabolomic and gene expression analyses. Calcium deposition was significantly enhanced by 0.3 mM hydrogen peroxide in the osteogenic media after 2 weeks, with minimal calcification in its absence. Similar results were observed in a medium transfer experiment using 3-day-old hydrogen peroxide-treated conditioned medium, which led to an increased expression of osterix and alkaline phosphatase. Metabolomic analysis revealed a gradual increase in ex-ATP and its metabolites, including ADP, AMP, and adenosine, in the medium. The metabolite increase was enhanced by hydrogen peroxide after 12 h. Moreover, exogenous adenosine (100 μM) increased mineralization in osteogenic media. Additionally, 1 μM dipyridamole, an inhibitor of equilibrative nucleoside transporter 1 (Ent1), also increased it in response to low-dose (0.1 mM) hydrogen peroxide. The enhanced osteogenic calcification of the tendon cell culture by hydrogen peroxide was associated with an increase in extracellular nucleotide metabolites, especially adenosine, with some evidence of causality.

The Socialist Republic of Vietnam, with a population of approximately 100 million, faces a critical shortage of ophthalmologists with only 1,300 practitioners nationwide (1.3 per 100,000 population). Cataracts remain the leading cause of blindness, accounting for over 75% of cases. While volunteer cataract surgery programs operate throughout the country, resource limitations often preclude comprehensive pre- and post-operative assessments, including standardized visual function testing. We report a case from a rural Vietnamese hospital, demonstrating significant objective visual improvement after cataract surgery, which highlights both the challenges and the public health significance of surgical outreach in resource-limited settings.An 86-year-old Vietnamese woman presented with vision loss and no documented medical or ophthalmic history. She underwent volunteer-based cataract surgery on her right eye. Preoperative findings included uncorrected visual acuity of 0.03 (20/667), intraocular pressure (IOP) of 13.0 mmHg, and a dense nuclear sclerotic cataract (grade 4-5) precluding fundoscopic examination. Phacoemulsification with intraocular lens (IOL) implantation was performed without complications. Postoperative management included topical antibiotics and overnight patching. On postoperative day one, the patient’s uncorrected visual acuity improved to 0.6 (20/33). IOP was 14.0 mmHg, and findings included mild anterior chamber inflammation, well-centered IOL, and a clear fundus view with normal macula and optic disc morphology.This case highlights that cataract surgery in a rural, low-resource setting can result in substantial visual improvement, even in advanced cases. It emphasizes cataracts as a leading cause of reversible blindness in Vietnam and demonstrates the transformative impact of surgical outreach. Expanding access and training are essential to address unmet ophthalmic needs in underserved regions.

The immune landscape of tumor-draining lymph nodes (TDLNs) plays a critical role in shaping antitumor responses and influencing prognosis in oral squamous cell carcinoma (OSCC). Among patients with lymph node (LN) metastasis, clinical outcomes vary widely, yet reliable biomarkers for prognostic stratification remain limited. This study aimed to identify immune features in tumors and LNs that differentiate between favorable and poor outcomes in OSCC patients with nodal metastasis. We analyzed T cell receptor (TCR) CDR3 repertoires and the expression of immune-related genes in primary tumors and paired sentinel LNs from OSCC patients who underwent tumor resection and lymphadenectomy. Patients were divided into three groups: Group A (no nodal metastasis), Group B1 (metastasis without recurrence), and Group B2 (metastasis with recurrence). TCR diversity was assessed using the Shannon index. The expression of immune-related genes (e.g., CD3E, CD4, CD8B, FOXP3, CTLA4, IL2, IL4) was measured by quantitative PCR and normalized to GAPDH. TCR diversity was lower in tumors than in non-metastatic LNs, reflecting clonal expansion. Metastatic LNs exhibited tumor-like diversity, suggesting infiltration by tumor-reactive clones. Tumor gene expression did not differ across groups, but LNs from metastatic cases showed the reduced expression of several immune genes. Notably, CD3E, CD8B, CTLA4, IL2, and IL4 distinguished B1 from B2. The immune profiling of LNs offers superior prognostic value over tumor analysis in OSCC patients with LN metastasis. LN-based evaluation may aid in postoperative risk stratification and personalized postoperative management and could inform decisions regarding adjuvant therapy and follow-up strategies.

Patients with glaucoma often require long-term use of multiple ophthalmic medications, which can make adherence to additional treatments, such as anti-allergic eye drops for seasonal allergic conjunctivitis, particularly challenging. Moreover, corticosteroid eye drops or ointments, commonly used to manage ocular allergy, are generally avoided in these patients due to the risk of increasing intraocular pressure. We report a case in which a patient with glaucoma, already undergoing multiple topical therapies, experienced recurrent allergic conjunctivitis and blepharitis each spring. The use of conventional anti-allergic eye drops had limited efficacy due to poor adherence associated with the complexity of the treatment regimen. To address this, a newly introduced epinastine cream was applied to the eyelids once daily as an alternative treatment. Following this change, the patient's allergic ocular symptoms improved substantially, with enhanced treatment compliance and no adverse effects on intraocular pressure during follow-up. This case suggests that non-ocular-drop formulations, such as eyelid creams, may offer a practical and effective approach for managing allergic eye disease in patients with glaucoma who are already on complex topical regimens.

BackgroundPeriodontal inflamed surface area (PISA) and masticatory efficiency have been used to evaluate the relationship between systemic diseases and oral diseases. However, clear standards for PISA values and masticatory efficiency in relation to the severity of periodontitis are lacking. This study aims to evaluate PISA values and masticatory efficiency based on the 2018 periodontal status classification system.MethodsIn total, 153 healthy participants diagnosed with periodontitis were included in the study. The diagnosis was based on the 2018 periodontal status classification. PISA values and masticatory efficiency were measured at baseline and after initial periodontal therapy.ResultsPISA demonstrated a higher area under the curve for Stage III (0.815) and Grade B (0.85). At baseline, PISA was showed significant negative correlation with masticatory efficiency (B coefficient [95% CI]: -0.02 [-0.03, -0.006], p < 0.01). Following periodontal therapy, both PISA values and masticatory efficiency showed significant improvements, with median PISA values changing from 856 at baseline to 277.5 after treatment, and mean masticatory efficiency increasing from 153.3 to 166.9. After initial periodontal therapy, PISA values were significantly higher in patients classified as Stage IV and Grade C compared to those with other stages and grades. Age exhibited a significant negative correlation with changes in PISA (B coefficient [95%CI]: -11.8 [-20.3, -3.19]), and change in PISA value was significantly positively related to the increase in masticatory efficiency (B coefficient [95%CI], 0.02 [(0.0002, 0.03]). In patients with periodontitis, changes in periodontitis classification were associated with increased PISA values and decreased masticatory efficiency.ConclusionPeriodontal therapy improved PISA and masticatory efficiency values. However, the extent of improvement was less pronounced in patients with higher stages and grades of periodontitis. It is essential to consider the interplay between increased PISA and decreased masticatory efficiency when treating patients with severe periodontitis.

Background/Objectives: Jaw deformities affect not only facial aesthetics but also various oral functions. While previous studies have demonstrated that mandibular prognathism (MP) alters masticatory-induced brain blood flow (BBF), the temporal characteristics of these hemodynamic changes have remained unclear. In this cross-sectional observational study, we investigated the following two specific objectives: (1) whether food hardness affects not only the magnitude but also the temporal patterns of BBF changes during mastication and (2) how malocclusion is associated with these temporal hemodynamic responses. Methods: Twenty-six participants with normal occlusion (NORM) and twenty patients with MP participated in this study. BBF was measured using functional near-infrared spectroscopy, while participants chewed soft paraffin or hard gummy candy. Maximum oxygenated hemoglobin (oxy-Hb) values and time-to-peak BBF were analyzed. Results: While food hardness did not significantly affect maximum oxy-Hb within groups, the MP group showed significantly lower responses during hard gummy candy mastication compared to the NORM group. The occlusal contact area exhibited significant positive correlation with maximum oxy-Hb values, while the ANB angle, an indicator of intermaxillary skeletal relationship, showed no significant correlation with BBF parameters. The hard gummy candy/paraffin ratio of maximum oxy-Hb was significantly higher in the NORM group compared to the MP group. Time-to-peak BBF was approximately twice as long for hard gummy candy compared to paraffin in both groups, with no significant differences between groups. Conclusions: These findings reveal that while MP attenuates the magnitude of masticatory-induced BBF, particularly during hard food mastication, the temporal adaptation to increased food hardness is preserved. This dissociation between magnitude and timing effects suggests that intact basic neurovascular coupling mechanisms would be maintained even in the condition of altered masticatory function in a MP subject, which is providing new insights for rehabilitation strategies in orthognathic surgery cases.

IntroductionDementia can be prevented through early intervention; hence, there is an urgent need for biomarkers to help diagnose mild cognitive impairment (MCI).ObjectivesWe aimed to develop a multi-marker panel composed of plasma metabolites to aid in the diagnosis of MCI.MethodsWe performed an analysis of a multi-marker panel of MCI metabolites using a random forest algorithm with variable selection methods and a global surrogate with principal component analysis and partial least squares (PLS).ResultsBy incorporating variable selection methods, we constructed a predictive model that demonstrated robust performance, with an AUC of approximately 0.85 in both cross-validation and test evaluations, using only five metabolites (methionine, quinic acid, hypoxanthine, O-acetylcarnitine, and 2-oxoglutaric acid). However, owing to the limited number of selected metabolites, it was challenging to infer the biological meaning of this multi-marker panel. To interpret this multi-marker panel biologically, we constructed a global surrogate model using PLS. By examining the PLS loadings corresponding to the scores with intergroup differences, we identified a relationship between 14 metabolites involved in neuronal energy metabolism and neurotransmission. This suggests that the multi-marker panel constructed in this study is related to abnormalities in energy metabolism and neurotransmission in patients with MCI.ConclusionThe method used in this study may be broadly applicable for analyzing multi-marker panels of metabolites and their biological interpretation. This study included an independent validation, and further larger-scale studies using additional external cohorts are warranted to confirm the generalizability of this approach.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11306-025-02372-7.