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Background and Aims: Neuroinflammation, a low-grade chronic inflammation of the central nervous system, is linked to age-related neuropsychiatric disorders such as senile depression and Alzheimer's disease. Recent studies have explored controlling neuroinflammation as a novel treatment strategy. Molecular hydrogen shows anti-inflammatory effects. However, its impacts on neuroinflammation and age-related neuropsychiatric disorders remain unelucidated. We investigated molecular hydrogen's effects on microglial activation, neuroinflammation, depressive-like behavior, and short-term cognitive decline in senescence-accelerated mouse-prone 8 (SAMP8) mice., Methods: Six-week-old SAMP8 or senescence-accelerated mouse-resistant 1 (SAMR1) mice received hydrogen-rich jelly (HRJ) or placebo jelly (PJ) from six weeks of age for 26-28 weeks. Depressive-like behavior was assessed using tail suspension and forced swimming tests, while cognitive function was evaluated using the Y-maze and object recognition tests. Brain tissues were used for immunohistochemical studies or to measure pro-inflammatory cytokine levels via enzyme-linked immunosorbent assay (ELISA)., Results: HRJ intake reduced immobility time in both tail suspension and forced swimming tests and enhanced visual cognitive and spatial working memory in SAMP8 mice. Additionally, HRJ intake suppressed the 8-hydroxy-2'-deoxyguanosine (8-OHdG), Iba1, and cleaved caspase 3 expression levels in the medial prefrontal cortex and hippocampal dentate gyrus. Furthermore, HRJ intake significantly lowered IL-6 levels in brain tissues of SAMP8 mice., Conclusions: These findings suggest that molecular hydrogen treatment may regulate neuroinflammation induced by activated microglia and improve depressive-like behavior and short-term cognitive impairment in SAMP8 mice., Competing Interests: Declaration of Competing Interest Shinryo Corporation (Kitakyushu, Japan) provided partial support for this research., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Endoscopic treatment for second primary malignancies after esophagectomy has been increasingly performed; however, evidence regarding the outcomes of endoscopic submucosal dissection (ESD) for superficial cancer of the remnant esophagus after esophagectomy (SCREE) is limited., Methods: We retrospectively extracted cases of ESD for SCREE from our institutional database, which included 739 consecutive esophageal ESD procedures performed between January 2009 and September 2023. Information on prior treatment, clinical features of the lesions, and outcomes was evaluated., Results: Overall, 20 patients (median age: 74 years) with 27 lesions were enrolled. ESD was performed at a median of 15 months after esophagectomy. All lesions were flat, with a median tumor diameter of 12 mm. The median ESD procedure time was 70 min. En bloc resection was achieved for all 27 lesions, with one minor perforation complication. The R0 resection rate was 96% (26 of 27). Endoscopic balloon dilation (EBD) of the anastomotic site at the beginning of ESD was required in 30% (8 of 27) of the cases. Among them, EBD was significantly more frequently performed in cases after partial esophagectomy (64%, 7 of 11) than in cases after other types of surgery. The resection speed was significantly faster in lesions after total pharyngo-laryngo-esophagectomy and slower in lesions after subtotal esophagectomy, located in the upper region, and near the anastomosis., Conclusions: Our study demonstrated the feasibility of ESD for SCREE although EBD or a longer procedure duration may be required depending on the pre-ESD surgical technique and location of the lesions., Competing Interests: Declarations. Conflict of interest: All authors have no conflict of interest to disclose. Ethical statement: This study was conducted in accordance with the revised Declaration of Helsinki and approved by the ethics committee of our institution., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Poor blood pressure control in treated patients with hypertension is an important topic in the field of hypertension, and an unmet need for new therapeutic drugs remains. Soluble guanylate cyclase (sGC), a key signal transduction enzyme responsible for vasodilation, has attracted increasing interest as a therapeutic target in various cardiovascular diseases. Two different sGC agonists, sGC stimulators and activators, can increase its enzymatic activity in reduced and oxidized/apo forms, respectively. With some sGC agonists being already in clinical use, drugs in this category are expected to become new therapeutic agents for various conditions, including hypertension. In this review, we summarize the current knowledge on the antihypertensive effects of sGC agonists in various preclinical studies involving animal models of spontaneous hypertension, salt-sensitive hypertension, nitric oxide-deficient hypertension, renin-angiotensin-aldosterone system-dependent hypertension, malignant hypertension, metabolic syndrome, renoprival hypertension, renovascular hypertension, drug-induced hypertension, pregnancy hypertension, and treatment-resistant hypertension. Our compilation provides a comprehensive rationale for advancing the clinical development of sGC agonists for the treatment of hypertension., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

This study developed water-dispersible γ-oryzanol (WD-OZ) using microemulsion system and assessed their absorption in rats. While γ-oryzanol itself is hardly soluble in water, WD-OZ exhibited high water dispersibility, and γ-oryzanol, along with its metabolites, was detected in rat plasma. These findings provide a solid basis for future application of the microemulsion-based approach to enhance the bioavailability of γ-oryzanol in food., (© The Author(s) 2025. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background/Objectives : The effects of ageing on the diaphragm are unclear. This study examined the association between ageing and diaphragm thickness, thickening fraction (TF), and diaphragm excursion (DE) as assessed by ultrasonography after adjusting for other factors. The relationship between these parameters and maximal inspiratory pressure (MIP) was also investigated. Methods : From 2022 to 2024, ambulatory and communicative adult volunteers and outpatients were recruited from four Japanese medical institutions. Each participant's background factors (including height, weight, and underlying diseases) and pulmonary function test results were assessed. Diaphragm thickness, TF, and DE were evaluated using ultrasonography. Results : The study involved 230 individuals with a mean age of 55.5 years (older adults (65 years and over), n = 117; non-older adults, n = 113). In older adults, the diaphragm was thicker (2.1 vs. 1.7 mm, p < 0.001), and TF was lower (88.7% vs. 116.0%, p < 0.001), with no significant difference in DE. Multivariate linear regression analysis adjusted for sex, height, body mass index, and underlying diseases showed positive associations between age and diaphragm thickness ( p = 0.001), but not with TF or DE. MIP was positively associated with DE ( p < 0.001) but not with thickness or TF. Age was negatively associated with MIP, regardless of diaphragm thickness, TF, and DE (all p < 0.001). Conclusions : As the diaphragm thickens with age, neither thickness nor TF is associated with MIP; only DE is related to MIP. Additionally, ageing is negatively associated with MIP, independent of diaphragm thickness, TF, and DE. Diaphragm function should be assessed using DE rather than thickness or TF.

Lipid droplets (LDs) are organelles that store and supply lipids based on cellular needs. While mechanisms preventing oxidative damage to membrane phospholipids are established, the vulnerability of LD neutral lipids to peroxidation and protective mechanisms are unknown. Here, we identify LD-localized Ferroptosis Suppressor Protein 1 (FSP1) as a critical regulator that prevents neutral lipid peroxidation by recycling coenzyme Q10 (CoQ10) to its lipophilic antioxidant form. Lipidomics reveal that FSP1 loss leads to the accumulation of oxidized triacylglycerols and cholesteryl esters, and biochemical reconstitution of FSP1 with CoQ10 and NADH suppresses triacylglycerol peroxidation in vitro . Notably, polyunsaturated fatty acid (PUFA)-rich triacylglycerols enhance cancer cell sensitivity to FSP1 loss and inducing PUFA-rich LDs triggers triacylglycerol peroxidation and LD-initiated ferroptosis when FSP1 activity is impaired. These findings uncover the first LD lipid quality control pathway, wherein LD-localized FSP1 maintains neutral lipid integrity to prevent the buildup of oxidized lipids and induction of ferroptosis., Competing Interests: COMPETING INTERESTS J.A.O. is a member of the scientific advisory board for Vicinitas Therapeutics and has patent applications related to ferroptosis.

Hexafluoropropylene oxide dimer acid (HFPO-DA), which belongs to the class of perfluoroalkyl ether carboxylic acid (PFECA), is a new alternative to perfluorooctanoic acid (PFOA). However, whether HFPO-DA is a safer alternative to PFOA in neonates remains unclear. In this study, we evaluated neonatal hepatic toxicity on postnatal days 9-10 by orally exposing pregnant CD-1 mice to 0.3 or 3.0 mg/kg/day (low or high doses) of HFPO-DA or PFOA from gestation days 15-17. The results showed that exposure of pregnant mice to HFPO-DA and PFOA induced similar phenotypic effects, including significant decreases in neonatal body weight (BW) and significant increases in liver weight relative to BW in the high-dose. Notably, HFPO-DA exposure significantly decreased in neonatal BW in the low-dose group, whereas PFOA did not. Comprehensive gene expression analysis revealed significant alterations in 408 and 1402 differentially expressed genes (DEGs) in the liver of neonates from the low- and high-dose HFPO-DA groups, respectively, while PFOA significantly altered 0 and 292 DEGs in the corresponding groups. Gene set enrichment analysis indicated that the DEGs induced by HFPO-DA and PFOA were enriched in pathway related to "PPAR signaling", "fatty acid metabolism", and "biological oxidations". In addition, transactivation assays revealed that mouse (m)PPARα and mPPARγ activity of HFPO-DA exceeds that of PFOA and molecular docking simulations analysis predicted that the binding conformation differ between PFOA and HFPO-DA. Overall, our findings demonstrate that HFPO-DA consistently affected neonatal phenotypes, liver gene expression and the molecular initiating events involving PPARα/γ, at lower concentrations than PFOA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Aspiration pneumonia, which often recurs due to dysphagia, worsens as patients move between homes, facilities, and hospitals. The impact of pre-hospital living setting on oral intake at discharge remains unclear. The purpose of this study was to identify the effects of the pre-hospital living setting on the nutritional intake route upon discharge in older patients with aspiration pneumonia., Methods: This prospective cohort study included patients aged ≥ 65 years who were admitted to an acute care hospital and diagnosed with aspiration pneumonia. Patients were followed up until discharge or death during hospitalisation. Patient demographic information, pre-hospital living setting (home or nursing facility), functional oral intake scale (FOIS) score, pneumonia severity index, clinical frailty scale score, history of aspiration pneumonia, and pneumonia recurrence during hospitalisation were recorded. Binary logistic regression was used to assess the impact of the pre-hospital living setting on oral intake at discharge as the primary outcome., Results: Among the 89 included patients (52 males (58.4%); mean age, 84.8 ± 7.9 years), 39.3% (n = 35) had pneumonia recurrence during hospitalisation. The average follow-up period was 44.0 ± 36.6 days. The pre-hospital living setting was independently associated with the nutritional intake route upon discharge (odds ratio = 7.72, 95% confidence interval (95%CI) = 1.70-35.1, p = 0.008)., Conclusions: The pre-hospital living setting could serve as a good indicator of the nutritional intake route upon discharge. It is essential to optimize care in both nursing facilities and hospital settings when caring for older patients with aspiration pneumonia., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Ethics Committee of Juntendo Tokyo Koto Geriatric Medical Centre (approval no. 111 − 10) and was conducted in accordance with the Declaration of Helsinki. Sufficient explanation was provided to the patient in writing and orally, and written informed consent to participate was obtained from the patient or their family. Consent for publication: Sufficient explanation was provided to the patient in writing and orally, and written informed consent for publication was obtained from the patient or their family. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/Objectives : The diaphragm is important for respiration, but the effects of age-related muscle loss and sarcopenia on diaphragm function are unclear. We evaluated the associations of sarcopenia and skeletal muscle mass (SMM) with diaphragm function. Methods : This study was conducted at three Japanese hospitals from May 2023 to September 2024. The participants underwent bioelectrical impedance for SMM assessment, as well as pulmonary function tests. Diaphragm ultrasound was used to measure the thickness at functional residual capacity (FRC), thickening fraction (TF), and diaphragm excursion (DE) during deep breathing (DB), and their associations with sarcopenia and low skeletal muscle index (SMI) were analyzed. Results : Overall, 148 patients (mean age 78.1 years; sarcopenia, n = 35; non-sarcopenia, n = 103) were included. No statistically significant differences in thickness(FRC), TF and DE were observed between the sarcopenia group and the non-sarcopenia group. The low SMI group had significantly lower thickness (difference -0.22, 95% CI; -0.41, -0.29) and DE (difference -9.2, 95%CI; -14.0, -4.49) than the normal SMI group. Multivariable linear regression analyses adjusted for age, sex, and stature revealed no association between thickness (FRC) and sarcopenia ( p = 0.98), but thickness (FRC) was negatively associated with low SMI ( p = 0.034). DE during DB was negatively associated with sarcopenia ( p = 0.024) and low SMI ( p = 0.001). TF showed no associations. Conclusions : DE during DB was reduced in patients with sarcopenia and low SMI, and thickness (FRC) was reduced in those with low SMI without sarcopenia.

Purpose: To evaluate the significant findings of hip periprosthetic joint infection (PJI) using metal-artifact-reduction (MAR) MRI and to compare the MRI results to other clinical markers., Methods: The results of MRI, including two-dimensional fast-spin echo sequences with increased bandwidth and multi-acquisition variable-resonance image combination selective for hips with orthopedic implants at 1.5T (from April 2014 to November 2021), were retrospectively assessed for imaging findings and diagnostic impressions by two radiologists. Clinical data and courses were also investigated. Univariate and multivariate analyses were performed to identify the significant MRI findings in patients with hip PJI and those who underwent surgical intervention. The MRI impressions were compared with other clinical markers in diagnosing hip PJI., Results: Thirty-seven hip joints in 24 Asian patients (age = 73.9 ± 10.8 years; 18 females) were included. Twelve hip joints (32%) had PJI; seven underwent a surgical intervention. The significant findings for hip PJI included periosteal edema of the acetabulum, intermuscular edema, intramuscular fluid collection, and lymphadenopathy (P < 0.05). In the cases with surgical intervention, the significant findings included capsular distension, capsular thickening, an osteolysis-like pattern of the femur, subcutaneous fluid collection, and lymphadenopathy (P < 0.05). The MRI impressions had high diagnostic significance for both hip PJI cases and those with surgical intervention (P < 0.001). The MRI impression was more significant for hip PJI than the other clinical markers (P < 0.05), while the other clinical markers were more significant in the cases with surgical intervention (P < 0.05)., Conclusion: The significant findings in the hip PJI cases included acetabular periosteal edema, intermuscular edema, intramuscular fluid collection, and lymphadenopathy. The significant findings in the cases with surgical intervention included capsular distention, capsular thickening, a femoral osteolysis-like pattern, subcutaneous fluid collection, and lymphadenopathy. The utilization of MAR MRI demonstrated great diagnostic significance for hip PJI.

Nitric oxide (NO)-donor drugs, which stimulate reduced form of soluble guanylate cyclase (sGC), have different efficacy to the arteries and veins. This study examined whether sGC activators, which activate oxidized/apo sGC, also have arteriovenous selectivity similar to that of NO-donor drugs. The mechanical responses of the isolated blood vessels were assessed using the organ chamber technique and protein expression was verified using western blotting. BAY 60-2770 (sGC activator) caused concentration-dependent relaxation in both porcine coronary arteries and veins, with the response being slightly more pronounced in the arteries. In contrast, sodium nitroprusside (NO-donor drug)-induced relaxation of the arteries was slightly weaker than that of the veins. Vasorelaxant responses to 8-Br-cGMP (cGMP analog) did not differ between the arteries and veins. In the presence of ODQ (heme oxidant), the heterogeneities in the responses to BAY 60-2770 and sodium nitroprusside between the arteries and veins disappeared. The sGC expression in the arteries did not differ from that in the veins. These findings suggest that sGC activators, in contrast to NO-donor drugs, have greater effects on the arteries than on the veins. This may be due to differences in the balance of sGC forms expressed in the arteries and veins., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)