Objectives: The objective of this study was to compare the effects of time-restricted eating (TRE) alone and TRE combined with resistance exercise on inflammatory responses and oxidative stress levels in adults with obesity. Methods: Sixty adults who met the diagnostic criteria for obesity were randomly assigned to a control group (n = 20), a TRE group (n = 20), or a TRE plus resistance exercise group (n = 20). The TRE group underwent a 12-week TRE intervention, with an eating window from 08:00 to 16:00. Dietary composition was not modified, and total daily energy intake was maintained at baseline levels. During the remaining hours, participants strictly abstained from consuming energy-containing foods and beverages. In addition to the same TRE protocol, the combined intervention group performed elastic-band resistance exercise three times per week for 30–45 min per session. Those in the control group were instructed to maintain their usual sedentary behavior patterns and dietary habits, including food types and quantities, and to strictly avoid regular physical exercise throughout the trial. In all three groups, inflammatory markers (TNF-α, IL-4, IL-6, IL-10, sICAM-1, CRP, and IFN-γ) and oxidative stress markers (MDA, SOD, 8-OHdG, CAT, and TAC) were assessed before the intervention and after its completion. Changes in these markers were compared across the three groups, with TNF-α and MDA designated as the primary outcome measures. After completion of the trial, three participants were excluded from each group, leaving 17 participants per group for the final data analysis. Results: Before the intervention, no significant between-group differences were observed in TNF-α, IL-4, IL-6, IL-10, sICAM-1, CRP, IFN-γ, MDA, SOD, 8-OHdG, CAT, TAC, or energy intake (all p > 0.05). Compared with their respective baseline values, the TRE group showed significant reductions in TNF-α, MDA, and 8-OHdG levels and a significant increase in TAC levels (all p < 0.05). The combined intervention group showed significant reductions in TNF-α, IL-6, sICAM-1, MDA, and 8-OHdG levels and significant increases in IL-10, IL-4, SOD, and TAC levels (all p < 0.05). After the intervention, compared with the control group, the TRE and combined intervention groups had significantly lower levels of TNF-α, IL-6, sICAM-1, MDA, and 8-OHdG (all p < 0.05), whereas the combined intervention group had significantly higher levels of IL-10, IL-4, SOD, and TAC (all p < 0.05). In addition, IL-4 and SOD levels were significantly higher in the combined intervention group than in the TRE group after the intervention (both p < 0.05). No significant within- or between-group differences were observed for CRP, IFN-γ, CAT, or energy intake (all p > 0.05). Conclusions: TRE alone and TRE combined with elastic-band resistance exercise improved inflammatory responses and oxidative stress levels in people with obesity after 12 weeks; however, the overall effects of the two interventions did not differ significantly.
Background: Pneumonia is driven by disordered immune inflammation dominated by dysregulated macrophage polarization. Peimine, the major bioactive steroidal alkaloid of Fritillariae Bulbus, exerts anti-inflammatory and immunomodulatory effects, whereas its direct targets and the metabolic routes through which it may influence macrophage polarization in pneumonia remain unclear. Objectives: This paper explores, and prioritizes for experimental testing, how peimine may regulate macrophage polarization in pneumonia, by combining public transcriptomic data with explainable machine learning. Methods: Potential human protein targets of peimine were predicted from three independent databases and pooled as a union. Two GEO datasets (GSE42830, GSE65682; 80 controls and 200 patients) were corrected for batch effects, screened for pneumonia DEGs and deconvoluted with CIBERSORT to estimate M0/M1/M2 macrophage fractions. WGCNA identified macrophage-related modules and hub genes, which were intersected with peimine targets and DEGs. Ten shared genes entered 113 classifiers under a 7:3 stratified split, with normalization and feature selection fitted inside the training data; SHAP was used to rank features of a gradient-boosting surrogate model, and AutoDock Vina docking was used to generate structural hypotheses. Results: A total of 238 peimine targets and 2991 pneumonia DEGs were obtained, and the estimated M0, M1 and M2 fractions were all higher in pneumonia samples. The brown module was positively associated with M0 (r = 0.68) and M2 (r = 0.28) fractions and contained 4 M0-related and 6 M2-related shared genes, whereas no M1-related shared gene was identified. The RF + Lasso hybrid model achieved a test-set AUC of 0.999 in an internal random split. SHAP ranked UGCG, MMP8 and KLF5 highest among the M0 features and CCR3, ITK, S1PR5 and PRKCQ highest among the M2 features; all seven were differentially expressed, with single-gene AUCs of 0.763–0.983. Docking predicted favorable binding of peimine to CCR3, ITK, S1PR5, PRKCQ and MMP8 (estimated binding energies −10.6 to −7.6 kcal/mol), and pathway annotation linked UGCG and S1PR5 to sphingolipid and glucosylceramide metabolism. Conclusions: These computational analyses do not demonstrate efficacy; they generate the testable hypothesis that peimine may act through two complementary modules, a CCR3/ITK/S1PR5/PRKCQ module associated with M2-like programmes and an MMP8/UGCG/KLF5 module associated with M0-derived inflammation and matrix remodeling, with a possible sphingolipid metabolic link. Experimental validation is required.
Background/Objectives: Glutamine supplementation has been investigated across nutritional, clinical and preclinical settings, but the development and thematic structure of this literature have not been comprehensively mapped. This bibliometric study examined publication trends, leading contributors, citation patterns, international collaboration and thematic evolution. Methods: The Web of Science Core Collection was searched on 20 August 2026 using a title-based strategy targeting intervention-oriented glutamine research. The corpus comprised 1321 articles and reviews published during 1943–2025. Analyses were conducted in Python, including country co-authorship networks and author–keyword mapping. Co-occurrence and temporal analyses used author keywords from 925 publications (70.0%), with a 15-occurrence threshold for co-occurrence mapping and six thematic domains examined across four periods (1991–2025). Results: Publication output increased from the 1990s and peaked in 2014. The corpus spanned 512 sources and accumulated 42,356 citations (h-index 87). The United States, China and Brazil contributed the most publications, while the University of São Paulo was the leading institution. Clinical nutrition and critical illness, amino-acid metabolism, oxidative and inflammatory responses, intestinal function, exercise and oncology-related applications were represented. Clinical nutrition and critical illness decreased from 34.0% to 10.6% of keyword-bearing publications between the earliest and latest periods, while oxidative, inflammatory and immune responses increased from 16.0% to 21.1%. International co-authorship occurred in 17.3% of publications. Conclusions: The results demonstrate changing thematic representation and identify major contributors and collaboration patterns within intervention-oriented glutamine research. These descriptive findings do not establish clinical efficacy or the presence of substantive evidence gaps.
Background: Cardiovascular disease (CVD) remains the leading cause of mortality globally. The associations between composite indices integrating body composition and lipid-related metabolic characteristics and CVD remain insufficiently investigated. We therefore constructed the skeletal muscle-fat distribution metabolic index (SMFDMI) and explored its association with CVD. Methods: Data were derived from the China Health and Retirement Longitudinal Study. The prospective analysis included 6785 participants aged ≥45 years followed from 2011 to 2020, while the cross-sectional analysis included 8279 participants. Cox and logistic regression models, restricted cubic splines, subgroup analyses, and sensitivity analyses were performed. Results: The cohort and cross-sectional analyses included participants with median ages of 58 and 59 years and male proportions of 47.19% and 46.42%, respectively. In Model 3, higher SMFDMI was associated with a lower risk of incident CVD, with a 25% lower risk in Q5 than in Q1 (HR = 0.75, 95% CI: 0.63–0.89). The cross-sectional analysis also showed an inverse association with prevalent CVD. Restricted cubic splines suggested an approximately N-shaped nonlinear relationship between SMFDMI and CVD risk. Subgroup analyses showed a stronger inverse association in males (Q5 vs. Q1: HR = 0.62, 95% CI: 0.48–0.81) and in those without chronic diseases. An alternative index yielded similar findings. Conclusions: Higher SMFDMI was associated with a lower risk of incident CVD in middle-aged and older Chinese adults. SMFDMI may provide additional insights into the relationship between muscle health and cardiovascular health during aging, with potential relevance to primary healthcare.
Background/Objectives: Anthracycline-based chemotherapy is associated with systemic toxicities in patients with breast cancer. Aerobic exercise may help mitigate treatment-related effects, but its associated metabolic responses during chemotherapy remain poorly understood. This study assessed biochemical and circulating metabolomic responses to aerobic exercise during anthracycline-based chemotherapy. Methods: This exploratory secondary analysis included 40 participants from a randomized controlled trial (trained n = 21; control, n = 19). Participants in the trained group completed a 12-week aerobic exercise intervention during chemotherapy. Biochemical markers and untargeted plasma LC–MS metabolomic profiles were assessed before and after intervention. Exploratory metabolic candidates were evaluated using linear mixed-effects models with Benjamini–Hochberg correction. Results: Significant Group × Time interactions were observed for 10 of 12 physiological and biochemical markers after BH-FDR correction in the primary analysis. However, baseline-adjusted ANCOVA sensitivity analyses showed that only IL-6 retained statistical significance after BH-FDR correction (adjusted between-group difference: −15.58 pg/mL, 95% CI: −20.72 to −10.45; FDR < 0.001). Despite limited global metabolomic separation, sequential screening identified 26 candidate features, seven of which showed significant Group × Time interactions after correction across candidates. Five had putative annotations, including lysophosphatidylcholine (LPC) 14:1, lysophosphatidylethanolamine (LPE) 17:1, cis-7-hexadecenoic acid, L-ascorbate, and vitamin E acetate. In a full-feature sensitivity analysis, only Com_3317_pos remained significant after BH-FDR correction across all 1150 metabolic features (FDR = 0.0228). Conclusions: Aerobic exercise during anthracycline-based chemotherapy was associated with changes in circulating biochemical markers, although these findings were less robust after baseline adjustment. Untargeted metabolomics identified exploratory exercise-associated metabolic features, particularly those putatively related to lipid metabolism, but most did not remain significant after full-feature multiple-testing correction. Further validation is warranted.
