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Introduction: The internal thoracic artery is commonly used as a graft in coronary artery bypass grafting. In this study, we aimed to investigate whether papaverine prevents vasoconstriction caused by various vasospasm inducers, including 5-hydroxytriptamine or serotonin, in endothelium-denuded internal thoracic artery at concentrations as low as 1.25 mM used for radial arteries., Methods: Human internal thoracic artery tissue was obtained from patients (n=6) undergoing coronary artery bypass grafting. The organ bath technique was used to determine the inhibitory effects of papaverine on vasoconstriction induced by ergonovine, adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II in isolated endothelium-denuded internal thoracic artery. Moreover, the inhibitory effect of papaverine on collagen-stimulated human platelet aggregation was examined at the same concentration., Results: Papaverine inhibited ergonovine-induced vasoconstriction in a concentration-dependent manner. Papaverine at concentrations > 30 μM not only blocked ergonovine-induced vasoconstriction but also induced vasodilation. Papaverine at 30 μM significantly suppressed the vasoconstriction induced by 5-hydroxytriptamine or noradrenaline and completely blocked that induced by adenosine diphosphate or angiotensin II. However, 100 μM papaverine completely blocked the vasoconstriction induced by adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II. Additionally, papaverine significantly inhibited collagen-stimulated human platelet aggregation in a concentration-dependent manner., Conclusion: Overall, 100 μM papaverine prevented vasoconstriction by various vasospasm inducers, such as 5-hydroxytriptamine, and significantly suppressed collagen-stimulated platelet aggregation. These results suggest that papaverine at 100 μM, which is 1/10th the concentration used for radial artery, is sufficient to prevent vasospasm in internal thoracic artery during coronary artery bypass grafting.

Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective treatment of severe diabetic retinopathy (DR) and macular edema, but a significant subset of people showed inadequate response to anti-VEGF intervention. Since elevation or overexpressing retinol binding protein 3 (RBP3) decreased risks for retinal pathologies and progression to severe DR, we compared the therapeutic profile of RBP3 and anti-VEGF to normalize retinal dysfunctions induced by diabetes. Intravitreous injection of recombinant human RBP3 (rhRBP3) and anti-VEGF antibodies (bevacizumab) inhibited retinal vascular permeability in Lewis rats induced by VEGF-A or after 2 months of diabetes induced by streptozotocin, in parallel with reductions of retinal VEGF and VEGFR2 expressions and tyrosine phosphorylation of VEGFR. Only rhRBP3 ameliorated diabetes induced reduction of neural retinal function, measured by electroretinogram. Further, rhRBP3 reduced retinal expressions of inflammatory cytokines (TNFα and IL6) in retinal pigmented epithelial and Müller cells exposed to hyperglycemia. Metabolic studies, using Seahorse, showed only rhRBP3 normalized retinal glycolytic rates in diabetic rats. Thus, both intravitreous anti-VEGF antibodies and RBP3 injections normalized retinal vascular dysfunctions caused by diabetes. Only RBP3 targeted both neural and vascular retina to reduce glycolytic rates, reversed neural-retinal dysfunctions, and reduced inflammatory cytokines induced by diabetes, to delay early changes of DR., (© 2025 by the American Diabetes Association.)

Tissue engineering plays a pivotal role in the advancement of regenerative medicine. Thermoresponsive culture dishes, coated with specialized polymers that control cell adhesion through temperature fluctuations, enable the processing of cells into sheets for medical applications while maintaining their intact state. Cell sheets prepared using these culture dishes have been incorporated into several commercial pharmaceutical products. However, controlling the detachability of cell sheets using conventional thermoresponsive culture dishes remains a challenge, and often leads to unexpected detachment during cultivation. In this study, we developed a thermoresponsive culture dish with tunable cell detachability using a thermoresponsive block copolymer, poly(butyl methacrylate)- b -poly( N -isopropylacrylamide) (PBMA-PIPAAm), which is a specialized polymer that allows precise control of the amount of surface-immobilized polymer and polymer layer thickness. Culturing periodontal ligament-derived mesenchymal stem cells on these dishes demonstrated fully tunable detachability without compromising cell properties compared to conventional thermoresponsive dishes (UpCell®). Thermoresponsive PBMA-PIPAAm-coated culture dishes enable the complete on-demand detachment of transplantable cell sheets, thereby avoiding unexpected detachment that may increase production costs and reduce technical hurdles in the manufacturing process. The PBMA-PIPAAm coating method has the potential to contribute to biomedical and clinical applications of mesenchymal stem cell sheets., Competing Interests: T.O. is the founder and representative director of the board of CSTERM. T.O. is a founder and stakeholder at Cellseed, Inc. H.S. was engaged by CSTERM as the project leader of SSCW® development (until March 2023). Tokyo Medical and Dental University received research funding from the CSTERM. No potential conflicts of interest relevant to this article have been reported., (© 2025 The Author(s).)

Background & Aims: The Global Leadership Initiative on Malnutrition (GLIM) criteria has been recognised as major diagnostic criteria for malnutrition in adults worldwide; however, its validity in rehabilitation settings remains unclear. This study investigated the concurrent and predictive validity of the GLIM criteria for adult patients in convalescent rehabilitation wards., Methods: This retrospective cohort study was conducted using pre-established datasets from convalescent rehabilitation wards in a hospital. The inclusion criteria were adults aged ≥18 years admitted to the wards between November 2018 and October 2020 who were available for body composition assessment. Malnutrition diagnoses were determined by registered dietitians (RDs) using the GLIM criteria. The Subjective Global Assessment (SGA) was performed by another RD and used for the malnutrition reference standard. The GLIM criteria sensitivity and specificity were examined for SGA. The odds ratios and hazard ratios of GLIM-defined malnutrition for the total score of the Functional Independence Measure (tFIM) effectiveness and non-home discharge were calculated using univariable and multivariable logistic regression analyses and Cox proportional hazard models., Results: Data from 723 patients were extracted from the dataset. GLIM-defined malnutrition was confirmed in 207 (28.6%) patients, 87 (12.0%) with moderate malnutrition and 120 (16.6%) with severe malnutrition. The SGA graded 146 (20.2%) patients with moderate malnutrition (grade B) and 86 (11.9%) with severe malnutrition (grade C). The GLIM criteria (malnutrition/no malnutrition) had fair sensitivity (76.7%, 95% confidence interval [CI]: 70.7-82.0%) and good specificity (94.1%, 95% CI: 91.6-96.0%), indicating acceptable concurrent validity. GLIM-defined moderate malnutrition had poorer sensitivity than severe malnutrition (42.5% vs 81.4%). Logistic regression analyses revealed no evidence for the association between GLIM-defined malnutrition and poor tFIM effectiveness (adjusted odds ratio [AOR]: 1.09, 95% CI: 0.71-1.69) and non-home discharge (AOR: 1.19, 95% CI: 0.76-1.84). The Cox proportional hazard analyses also showed no effect of malnutrition on outcomes., Conclusion: The GLIM criteria had fair sensitivity and good specificity, indicating acceptable criteria for diagnosing malnutrition in rehabilitation settings. However, its predictive validity for functional recovery and discharge outcomes was insufficient., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Porphyromonas gingivalis is the most pathogenic periodontal bacterium in the world. Recently, P. gingivalis has been considered responsible for dysbiosis during the development of periodontitis. This study aimed to evaluate a novel immunochromatographic device using monoclonal antibodies against P. gingivalis in subgingival plaques. A total of 72 patients with chronic periodontitis and 53 periodontally healthy volunteers underwent clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis and compared using real-time polymerase chain reaction (PCR). In the periodontitis group, a significant positive correlation was observed between the test device scores and the real-time PCR results. The specificity, positive predictive value, negative predictive value, and accuracy of the test device for P. gingivalis , as determined by real-time PCR, were 98%, 94%, 89%, and 90%, respectively. There were significant differences in bacterial counts by real-time PCR among the groups with different ranges of device scores. Additionally, there was a significant positive correlation between the device scores for P. gingivalis and periodontal parameters. These results suggest that this novel immunochromatographic device can be effectively used for rapid detection and semi-quantification of P. gingivalis in subgingival plaques.

Aim: This retrospective cohort study investigated the relationship between sarcopenia and Activities of Daily Living capacity after discharge from convalescent rehabilitation wards., Methods: We included consecutive patients discharged from three convalescent rehabilitation wards in a hospital in Japan between December 2018 and October 2020. Sarcopenia was diagnosed based on the criteria of the 2019 Asian Working Group for Sarcopenia, utilizing skeletal muscle mass index and handgrip strength. Statistical analyses were carried out separately for men and women. The primary outcome was a higher motor domain (motor Functional Independence Measure [mFIM]) and a higher cognitive domain (cognitive Functional Independence Measure [cFIM]) of the FIM score 1 month after discharge. The secondary outcomes were higher mFIM and cFIM scores 6 months after discharge, analyzed using binary logistic regression., Results: Among 305 participants (mean age 70.0 years, 148 men), 93 were identified as having sarcopenia. The prevalence of sarcopenia was 16% for outpatient rehabilitation services, 59% for home-visit rehabilitation services and 50% for older adult day care. Logistic regression analyses showed that sarcopenia at discharge was not an independent variable for mFIM at 1 month (odds ratio [OR] 20, 95% confidence interval [CI] 0.31-1300 for men, OR 0.51, 95% CI 0.11-2.4 for women) and cFIM (OR 0.63, 95% CI 0.10-3.8 for men, OR 5.3, 95% CI 0.81-34 for women). At 6 months, sarcopenia at discharge was not an independent variable for mFIM (OR 0.30, 95% CI 0.02-3.6 for men, OR 0.40, 95% CI 0.06-2.5 for women) and cFIM (OR 0.16, 95% CI 0.01-2.4 for men, OR 0.00, 95% CI 0.00-1.1 for women)., Conclusions: Sarcopenia at the time of discharge from convalescent rehabilitation wards does not independently predict FIM 1 month or 6 months after discharge. Geriatr Gerontol Int 2024; 24: 715-721., (© 2024 Japan Geriatrics Society.)

Insulin resistance and hyperglycemia are risk factors for periodontitis and poor wound healing in diabetes, which have been associated with selective loss of insulin activation of the PI3K/Akt pathway in the gingiva. This study showed that insulin resistance in the mouse gingiva due to selective deletion of smooth muscle and fibroblast insulin receptor (SMIRKO mice) or systemic metabolic changes induced by a high-fat diet (HFD) in HFD-fed mice exacerbated periodontitis-induced alveolar bone loss, preceded by delayed neutrophil and monocyte recruitment and impaired bacterial clearance compared with their respective controls. The immunocytokines, CXCL1, CXCL2, MCP-1, TNFα, IL-1β, and IL-17A, exhibited delayed maximal expression in the gingiva of male SMIRKO and HFD-fed mice compared with controls. Targeted overexpression of CXCL1 in the gingiva by adenovirus normalized neutrophil and monocyte recruitment and prevented bone loss in both mouse models of insulin resistance. Mechanistically, insulin enhanced bacterial lipopolysaccharide-induced CXCL1 production in mouse and human gingival fibroblasts (GFs), via Akt pathway and NF-κB activation, which were reduced in GFs from SMIRKO and HFD-fed mice. These results provided the first report that insulin signaling can enhance endotoxin-induced CXCL1 expression to modulate neutrophil recruitment, suggesting CXCL1 as a new therapeutic direction for periodontitis or wound healing in diabetes., Article Highlights: The mechanism for the increased risks for periodontitis in the gingival tissues due to insulin resistance and diabetes is unclear. We investigated how insulin action in gingival fibroblasts modulates the progression of periodontitis in resistance and diabetes. Insulin upregulated the lipopolysaccharide-induced neutrophil chemoattractant, CXCL1, production in gingival fibroblasts via insulin receptors and Akt activation. Enhancing CXCL1 expression in the gingiva normalized diabetes and insulin resistance-induced delays in neutrophils recruitment and periodontitis. Targeting dysregulation of CXCL1 in fibroblasts is potentially therapeutic for periodontitis and may also improve wound healing in insulin resistance and diabetes., (© 2023 by the American Diabetes Association.)

Background: The effect of sarcopenia on the recovery of swallowing function, and the interaction among sarcopenia, nutrition care, and rehabilitation therapy are inconclusive., Methods: This multicenter cohort study was conducted between November 2018 and October 2020 in convalescent rehabilitation hospitals in Japan and included post-stroke patients aged ≥65 years with dysphagia. All participants were assigned to sarcopenia and non-sarcopenia groups. The primary outcome was the achievement of ≥2 Food Intake Level Scale [FILS] gain, and the secondary outcomes included Functional Independence Measure (FIM) gain and efficiency. Considering the effect modification of energy intake and rehabilitation duration, logistic regression analyses were performed., Results: Overall, 153 participants with (median age, 82 years; 57.5% women) and 40 without (median age 75 years; 35.0% women) sarcopenia were included. The non-sarcopenia group had more patients who achieved an FILS gain of ≥2 (75.0%) than the sarcopenia group (51.0%). Sarcopenia was independently associated with a poor FILS gain (odds ratio:0.34, 95% confidence intervals: 0.13-0.86) but not associated with FIM gain or efficiency. This association was not affected by the rehabilitation duration or energy intake., Conclusions: In conclusion, sarcopenia was negatively associated with the recovery of swallowing function in stroke patients without interaction by energy intake and rehabilitation duration.

Objectives: This study aimed to investigate the association between muscle strength and adjusted appendicular skeletal muscle mass (ASM) in patients who have had strokes with the Functional Independence Measure (FIM) and the probability of being discharged., Methods: A retrospective cohort study was conducted for older patients who have had strokes admitted to convalescent rehabilitation wards between January 2017 and October 2020. Hand-grip strength (HGS) was used to assess muscle strength. ASM was measured with a bioelectrical impedance analysis, and then divided by height-squared, body weight, body mass index (BMI), body fat mass (BFM), and body fat percentage (BFP) to calculate the adjusted ASM. The primary outcome was FIM at the time of discharge, and the secondary outcome was the probability of being discharged to their home. Multivariate analyses were conducted to adjust for confounding effects., Results: The data of 699 participants (female: 47%; median age, 79 y) were analyzed. HGS was independently associated with FIM at the time of discharge in men (partial regression coefficient [B] = 0.482; 95% confidence interval [CI], 0.225-0.740) and women (B = 0.664; 95% CI, 0.263-1.065) and also was independently associated with being discharged to their home in men (odds ratio [OR]: 1.070; 95% CI, 1.030-1.100) and women (OR: 1.070; 95% CI, 1.000-1.130). Conversely, none of the adjusted ASM indices were associated with the outcomes. The cutoff value of HGS for discharge to home was 15.1 kg for men and 9.5 kg for women., Conclusions: In patients who have had strokes, HGS independently predicted FIM at the time of discharge and the probability of being discharged to their home. The adjusted ASM methods had less predictive value for functional and discharge outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)