Introduction: O-GlcNAcylation, a reversible post-translational modification regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is involved in various cellular processes, such as proliferation, differentiation, and inflammation modulation. Developmental study revealed that proper O-GlcNAcylation mediated by OGT is vital for tooth morphogenesis. However, the function of O-GlcNAcylation during reparative dentin formation is still unknown. To understand its therapeutic relevance in regenerative dentistry, we examined the potential of OGA inhibitor, Thiamet-G, in reparative dentin formation using both in vitro and in vivo approaches.
Methods: Human dental pulp stem cells were cultivated to examine cell viability, alkaline phosphatase (ALP) activity, and mRNA expression of reparative dentin-related genes. Furthermore, the dental pulp of the upper first molar in 8-week-old male ICR mice was exposed, and Thiamet-G was locally delivered for in vivo studies. Histological and immunohistochemical alterations were analyzed after 3 and 5 days post-cavity preparation, and dentin-bridge formation was evaluated at 42 days using histology and micro-CT.
Results: In vitro, Thiamet-G treatment facilitated proliferation, ALP activity, and upregulated expression of reparative dentin-related genes, including BMP2, BSP, DSPP, OCN, and RUNX2. In vivo, Thiamet-G treated specimens showed the altered localizations of NESTIN, NF-κB, MPO, OPN, RUNX2, TGF-β1, and TNF-α at 3 and 5 days post exposure, suggesting enhanced dentin regeneration and modulated inflammation. Particularly, at 42 days, Thiamet-G treated specimens exhibited enhanced dentin-bridge formation, confirmed by micro-CT imaging and histology.
Conclusion: Thiamet-G treatment facilitated reparative dentin formation by modulating inflammation and regulating regenerating signaling, suggesting its potential as a therapeutic agent.
Objectives: Both sleep deprivation (SD) and light at night have negative effects on human health and performance. The aim of our work was to compare the intermediate effects of total SD under two lighting conditions: full indoor lighting and darkness mimicking natural nocturnal wakefulness.
Methods: We examined melatonin levels during SD nights, locomotor activity and peripheral temperature rhythms, cognitive performance, mood, hunger, glycaemia and food preference after SD and recovery sleep. Statistical evaluation included ANOVA with FDR correction and confidence intervals.
Results: SD transiently altered peripheral temperature rhythm and post-SD activity, with faster resynchronisation after SD in darkness. Subjective sleepiness increased after SD, with light at night alleviating morning sleepiness. Positive affect decreased after SD but normalised after recovery sleep in both groups. Negative affect worsened in the morning after SD in darkness. Cognitive performance declined after SD, but this effect was higher after SD in darkness. Preprandial glycaemia was higher after recovery sleep following SD in darkness, and sweet taste preference was significantly higher after SD in darkness.
Conclusion: Light exposure during SD may lead to lower subjective sleepiness and better cognitive performance the next morning compared to SD in darkness. However, light during SD also causes more pronounced and persistent disruptions to circadian rhythms of temperature and activity. This underscores the trade-off between the short-term benefits of nocturnal light exposure and its potential long-term impacts on circadian health.
Background: The association between Omega-3 (ω-3)and non-alcoholic fatty liver disease (NAFLD) in individuals with normal fasting lipid levels subjects is unclear. In addition, few studies have explored whether postprandial triglyceride levels (PTG) mediates the association between ω-3 and NAFLD. We aimed to analyze the mediating effect of PTG on ω-3 and NAFLD.
Methods: In March 2024, volunteers were recruited from the Hebei Provincial People's Hospital. In total, 108 volunteers met the inclusion criteria. The basic information and biochemical parameters, as well as ω-3 and PTG were collected. NAFLD was diagnosed according to abdominal ultrasonography. The clinical characteristics of the participants was analyzed by quartiles of ω-3 (O1-O4 quartiles) and PTG (P1-P4 quartiles), respectively. Pearson correlation analysis was performed to investigate the correlation between ω-3 and PTG. Multivariate logistic regression analysis was applied to analyze the effect of ω-3 and PTG on NAFLD. Bootstrap was conducted to explore whether PTG mediated the association between ω-3 and NAFLD.
Results: Pearson correlation analysis indicated that ω-3 was negatively associated with PTG. Multivariate logistic regression analysis indicated that compared to the low ω-3 group, the risk of NAFLD significantly decreased in high ω-3 group [OR = 0.024 (0.006 ∼ 0.104)]. Mediating effect analysis showed that ω-3 significantly directly influenced NAFLD prevalence [β = -0.077, 95%CI (-0.128, -0.026)], and PTG partly mediated the indirect effect of the ω-3 on NAFLD prevalence [β = -0.084, 95%CI (-0.130, -0.037)], and the mediating effect accounted for 52.17% of the total effects.
Conclusion: In this cross-sectional analysis, both ω-3 and PTG were predictors of NAFLD, and PTG partly statistically mediated the indirect effect of the ω-3 on NAFLD prevalence.
Background: Hemodialysis, the principal therapy for end-stage renal disease (ESRD), directly influences pulmonary mechanics by alleviation of fluid overload and uremic toxin accumulation. Hemodialysis (HD), the main renal replacement therapy, removes excess volume and solutes, but its acute effects on pulmonary function remain uncertain. This meta-analysis evaluates impact of hemodialysis on pulmonary function and examines pre-to post-dialysis changes in spirometric parameters among ESRD patients.
Methods: We conducted meta-analysis of cross-sectional studies that measured pulmonary function in ESRD patients on maintenance hemodialysis. Data from 16 eligible studies (n = 719 patients) were synthesized. Our analysis was focused on changes in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, forced expiratory flow at 25%-75% (FEF25-75), and peak expiratory flow rate (PEFR). Statistical analysis was performed using random-effects models to calculate pooled mean differences (MD) for spirometric outcomes.
Results: Hemodialysis was associated with significant improvements in percent-predicted FEV1 (+8.99%) and FVC(+12.87%), while absolute changes in these parameters were small and not statistically significant. The FEV1/FVC ratio and PEFR also improved in percent-predicted terms. Sensitivity analyses confirmed stability of results, though high heterogeneity (I2>75%) was observed for several outcomes. Publication bias was minimal, with Egger's and Begg's tests indicating no significant asymmetry, except for borderline Begg's p-value for FVC (%pred). These improvements likely reflect ultrafiltration-mediated relief of pulmonary congestion and modulation of uremic milieu.
Conclusion: Hemodialysis acutely mitigates renal failure-related pulmonary restriction, with percent-predicted spirometry showing consistent gains. These effects highlight role of dialysis prescriptions and fluid management strategies in optimizing respiratory as well as renal outcomes.
Introduction: With the rising prevalence of obesity, time-efficient high-intensity exercises like Tabata training have gained significant attention for weight management. However, the effects of fasting versus post-breakfast states on substrate metabolism and energy expenditure during Tabata exercise remain unclear. This study aimed to investigate the metabolic responses to Tabata exercise under fasting and post-breakfast conditions in women, providing insight into how nutritional status acutely influences substrate utilization and energy expenditure.
Methods: Eighteen young normal-weight women (age 25.3 ± 3.1 years; BMI 20.9 ± 1.1 kg/m2)completed a randomized counterbalanced crossover trial, performing a 4-min Tabata workout under fasting (11-15 h overnight fast) and post-breakfast (90 min after a standardized meal) conditions. Gas exchange was continuously monitored to calculate fat oxidation, glucose oxidation, and energy expenditure.
Results: Fat oxidation was significantly higher in the fasting condition at all analyzed time points, with the largest difference observed at 60 s (1.05 ± 0.18 vs. 0.61 ± 0.07 g/min, p < 0.001). In contrast, glucose oxidation was consistently higher in the post-breakfast condition, peaking at 150 s (3.65 ± 0.52 vs. 3.38 ± 0.46 g/min, p < 0.001). Total energy expenditure was also greater post-breakfast, reaching 10.18 ± 0.29 kcal/min at 120 s compared with 9.70 ± 0.39 kcal/min in the fasting condition (p < 0.001).
Conclusion: Fasting and post-breakfast conditions elicit distinct acute metabolic responses during Tabata exercise in women. Fat oxidation was higher in the fasting state, while glucose oxidation and total energy expenditure were consistently higher in the post-breakfast state.
Purpose: This study aimed to investigate the acute responses induced by a session of repeated-sprint training in hypoxia (RSH) induced by voluntary hypoventilation at low lung volume (VHL) performed continuously throughout the exercise in healthy females.
Methods: Thirteen females performed, in a randomized order, two sessions of repeated sprints (three sets of eight 10-s all-out sprints): with normal breathing (RSN) vs. with VHL performed continuously throughout each set (RSH-VHL). Peak and mean power output, heart rate, stroke volume, cardiac output, pulse oxygen saturation, muscle oxygenation in the vastus lateralis and the biceps brachii, blood lactate concentration, rate of perceived exertion and perceived difficulty of breathing and pedalling were assessed.
Results: RSH-VHL did not induce desaturation (97.5 ± 2.0 for RSH-VHL vs. 98.0% ± 1.6% for RSN; p = 0.243) nor greater muscle deoxygenation in the vastus lateralis (mean minimum tissue saturation index: 62.3% ± 4.3% vs. 61.5% ± 4.4%; p = 0.193) or the short head of the biceps (36.6% ± 10.0% vs. 34.2% ± 13.7%; p = 0.320). Significantly lower training load indices were observed from the first set onwards during RSH-VHL compared with RSN: mean peak power output (311 ± 45 vs. 382 ± 46 W; p < 0.001) and blood lactate concentration (6.8 ± 2.9 vs. 9.9 ± 3.0 mmol/L; p = 0.003). The perceived difficulty of breathing was higher during RSH-VHL than RSN from the first set onwards (8.2 ± 2.2 vs. 6.0 ± 0.9; p = 0.022).
Conclusion: This study showed that, although participants reported increased breathing difficulty during RSH-VHL performed continuously, this condition did not result in significant systemic or local hypoxia. Moreover, it led to a lower training load compared to RSN. When VHL is performed continuously throughout each set, rather than only during sprints, it may be too strenuous, inducing a significant reduction in training load.
Background: To compare the effects of various exercise modalities on intelligence and determine the optimal exercise dose for children and adolescents.
Methods: A systematic review and Bayesian network meta-analysis following PRISMA guidelines was conducted. Four databases were searched up to 1 April 2025. Eligible RCTs involved participants aged 5-18 years and assessed exercise interventions with intelligence outcomes (general, fluid, or crystallized). Standardized mean differences (SMDs) with corresponding 95% confidence interval or credible intervals were calculated. Dose-response relationships were analyzed using model-based network meta-analysis.
Results: Fifteen RCTs with 3,400 participants were included. Exercise was linked to small-to-moderate improvements in general (SMD = 0.59), fluid (SMD = 0.43), and crystallized intelligence (SMD = 0.64). Dual-task balance training (DTBT) produced the most consistent and significant benefits across all domains. Yoga and multi-component exercise also showed positive effects. Optimal outcomes were achieved with sessions lasting ≥117.7 min, three times weekly, totaling 220 min per week for at least 11.12 weeks. An inverted U-shaped dose-response curve indicated diminishing returns beyond the optimal frequency and duration.
Conclusion: DTBT is the most effective exercise modality for improving intelligence in children and adolescents. The findings provide evidence-based guidance for designing school and clinical exercise programs to support cognitive development during growth.
Objective: This meta-analysis aimed to systematically evaluate the effects of post-activation potentiation enhancement (PAPE) on jump performance and explore its optimal induction strategies.
Methods: Randomized controlled trials (RCTs) investigating the influence of PAPE training on jump performance were retrieved from Web of Science, PubMed, Scopus, and EBSCO. Literature screening was conducted using the Cochrane Risk of Bias Tool. Quality assessment and statistical analyses were performed using RevMan 5.4 software, while sensitivity analysis and funnel plots were employed to evaluate result stability and publication bias.
Results: A total of 22 RCTs involving 468 participants were included. The meta-analysis demonstrated that PAPE significantly improved jump performance [SMD = 1.36, 95% CI (0.89, 1.83), P < 0.0001]. Subgroup analysis indicated that exercise intensity might be a source of heterogeneity across studies.The largest effect sizes with statistical significance were observed in the following subgroups: exercise mode (Back squat) [SMD = 2.85, 95% CI (0.98, 4.73), P = 0.003], gender (Male) [SMD = 1.53, 95% CI (0.92, 2.14), P < 0.0001], outcome extracted (Counter movement jump) [SMD = 1.34, 95% CI (0.86, 1.81), P < 0.0001], exercise intensity (Moderate Intensity) [SMD = 2.46, 95% CI (1.71, 3.22), P < 0.0001], and rest interval (3-7 min) [SMD = 1.47, 95% CI (0.79, 2.14), P < 0.0001].
Conclusion: PAPE may serve as a potentially effective strategy for enhancing jumping performance under appropriate conditions. In exercises aimed at improving jumping performance, back squats and medium-intensity induction appear to yield the most pronounced benefits. A 3-7 min recovery interval works best, though adjustments should be made based on individual exercise factors.
Systematic review registration: http://inplasy.com, identifier INPLASY202430008.
Metabolic dysfunction-associated steatohepatitis (MASH) is an increasing public health concern for which new therapies are urgently needed. As growing evidence suggests that the advanced glycation/lipoxidation end products (AGE/ALE) pathway contribute to disease progression, we investigated how pyridoxamine modulates hepatic AGE/ALE-related signaling in a murine model of MASH, as well as its pharmacological impact on key features of MASH. C57BL/6 mice were fed either a standard diet (Control) or a high-fat, high-carbohydrate diet with 2% cholesterol (HFHC + CHOL2%) for 12 weeks. From weeks 6-12, subgroups of both diet groups received pyridoxamine (200 mg/kg/day), while the remaining mice received vehicles. Body and liver weights, blood glucose levels, adipose tissue distribution, liver histology, serum biochemistry, microcirculation, inflammatory cytokines, oxidative stress, and AGE/ALE signaling were assessed. The HFHC + CHOL2% group showed marked steatosis, inflammation, and impaired hepatic microcirculation. Pyridoxamine treatment attenuated metabolic and hepatic changes, reducing weight gain, hyperglycemia, fat accumulation, steatosis, collagen deposition, and the expression of proinflammatory cytokines associated with MASH. Pyridoxamine significantly reduced systemic levels of reactive dicarbonyls, such as glyoxal and 3-deoxyglucosone, and prevented the accumulation of fluorescent AGE/ALE and CML in both serum and liver. In addition, in the liver, pyridoxamine downregulates RAGE, CD36, and galectin-3 receptors, while upregulating detoxifying mediators, including AGE-R1 and glyoxalase-1. In this context, the metabolic and hepatoprotective effects of pyridoxamine appear to be associated with a rebalancing of key components of the AGE/ALE signalling pathway, potentially attenuating the toxic feedback loop that contributes.
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