Physical fatigue (peripheral fatigue), which affects a considerable portion of the world population, is a decline in the ability of muscle fibers to contract effectively due to alterations in the regulatory processes of muscle action potentials. However, it lacks an efficacious therapeutic intervention. The present study explored bioactive compounds and the mechanism of action of Citrus reticulata peel (CR-P) in treating physical fatigue by utilizing network pharmacology (NP), molecular docking, and simulation-based molecular dynamics (MD). The bioactive ingredients of CR-P and prospective targets of CR-P and physical fatigue were obtained from various databases. A PPI network was generated by the STRING database, while the key overlapping targets were analyzed for enrichment by adopting KEGG and GO. The binding affinities of bioactive ingredients to the hub targets were determined by molecular docking. The results were further validated by MD simulation. Five bioactive compounds were screened, and 56 key overlapping targets were identified for CR-P and physical fatigue, whereas the hub targets with a greater degree in the PPI network were AKT1, TP53, STAT3, MTOR, KRAS, HRAS, JAK2, IL6, EGFR, and ESR1. The findings of the enrichment analysis indicated significant enrichment of the targets in three key signaling pathways, namely PI3K-AKT, MAPK, and JAK-STAT. The molecular docking and MD simulation results revealed that the bioactive compounds of CR-P exhibit a stronger affinity for interacting with the hub targets. The present work suggests that bioactive compounds of CR-P, specifically Hesperetin and Sitosterol, may ameliorate physical fatigue via the PI3K-AKT signaling pathway by targeting AKT1, KRAS, and MTOR proteins.

Type 2 diabetic osteoporosis (T2DOP) is a common complication in diabetic patients that seriously affects their health and quality of life. The pathogenesis of T2DOP is complex, and there are no targeted governance means in modern medicine. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese medicine that has a long history and has been used in the treatment of osteoporosis diseases. However, the molecular mechanism for the CRP treatment of T2DOP is not clear. Therefore, this study aimed to explore the underlying mechanisms of CRP for the treatment of T2DOP by using network pharmacology and molecular modeling techniques. By retrieving multiple databases, we obtained 5 bioactive compounds and 63 common targets of bioactive compounds with T2DOP, and identified AKT 1, TP 53, JUN, BCL 2, MAPK 1, NFKB 1, and ESR 1 as the core targets of their PPI network. Enrichment analysis revealed that these targets were mainly enriched in the estrogen signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway in diabetics, which were mainly related to oxidative stress and hormonal regulation. Molecular docking and molecular dynamics simulations have shown the excellent binding effect of the bioactive compounds of CRP and the core targets. These findings reveal that CRP may ameliorate T2DOP through multiple multicomponent and multitarget pathways.

Sarcopenia is a systemic medical disorder characterized by a gradual decline in muscular strength, function, and skeletal muscle mass. Currently, there is no medication specifically approved for the treatment of this condition. Therefore, the identification of new pharmacological targets may offer opportunities for the development of novel therapeutic strategies. The current in silico study investigated the active ingredients and the mode of action of Citri Reticulatae Pericarpium (CRP) in addressing sarcopenia. The active ingredients of CRP and the potential targets of CRP and sarcopenia were determined using various databases. The STRING platform was utilized to construct a protein–protein interaction network, and the key intersecting targets were enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Molecular docking was used to determine the binding interactions of the active ingredients with the hub targets. The binding affinities obtained from molecular docking were subsequently validated through molecular dynamics simulation analyses. Five active ingredients and 45 key intersecting targets between CRP and sarcopenia were identified. AKT1, IL6, TP53, MMP9, ESR1, NFKB1, MTOR, IGF1R, ALB, and NFE2L2 were identified as the hub targets with the highest degree node in the protein–protein interaction network. The results indicated that the targets were mainly enriched in PIK3-AKT, HIF-1, and longevity-regulating pathways. The active ingredients showed a greater interaction affinity with the hub targets, as indicated by the results of molecular docking and molecular dynamics simulations. Our findings suggest that the active ingredients of Citri Reticulatae Pericarpium, particularly Sitosterol and Hesperetin, have the potential to improve sarcopenia by interacting with AKT1 and MTOR proteins through the PI3K-AKT signaling pathway.

Prior research has demonstrated equivocal associations between selenium (Se) concentrations and osteoporosis (OP), yielding inconclusive findings. The purpose of the current study was to examine the potential correlation between Se levels and the risk of OP by using the Mendelian randomization (MR) study design. The genetic variants related to Se levels were obtained from a meta-analysis of a Genome-Wide Association Study (GWAS) conducted on toenail Se levels (n = 4162) and blood Se levels (n = 5477). The data summary for OP and bone mineral density (BMD) was obtained by utilizing the GWAS database. To examine the association between Se levels and BMD and OP, we employed three statistical methods: inverse variance weighted, weighted median, and MR-Egger. The reliability of the analysis was verified by sensitivity testing. All three methods of MR analysis revealed that Se levels had no effect on OP risk. In addition, the sensitivity analysis revealed no heterogeneity or pleiotropy, and the significance of the overall effect remained unaffected by single-nucleotide polymorphisms (SNPs), as determined by the leave-one-out analysis, indicating that our findings are relatively reliable. The results of our study indicate that there is no causal association between Se levels and the risk of OP. However, additional investigation is necessary to ascertain whether there is a potential association between these variables.

Background: Type 2 diabetes mellitus (T2DM) is a major global public health challenge. Aerobic exercise (AE) can be a key strategy for non-pharmacological intervention in T2DM through multi-targeted modulation of glucose and lipid metabolism, inhibition of chronic inflammation, and reduction of oxidative stress. This study aims to investigate the current status of AE intervention in T2DM research and analyze its future evolution. Methods: Using the R-based bibliometric software package and the Java-based visualization software CiteSpace and VOSviewer, we analyzed the literature and cited references related to AE intervention in T2DM research included in the Web of Science Core Collection (WOSCC) and China National Knowledge Infrastructure (CNKI) from 2014 to 2024. Results: This study included a total of 882 relevant literature sources (488 of which were indexed in WOSCC and 394 in CNKI). From the perspective of research trends, the number of literature sources on AE interventions for T2DM has shown fluctuating changes over time. In terms of research output, the United States, China, and Canada are at the forefront. It is worth noting that, although China has a relatively high number of published papers, there is still a significant gap in terms of the depth of international collaboration and the presentation of results in top-tier journals. Among researchers, Dai Xia (China) and Riddell MC (Canada) are the scholars with the highest number of published articles in this field. Keyword analysis indicates that mechanisms such as oxidative stress, insulin resistance, inflammatory responses, and glucose metabolism disorders remain core research hotspots. Time-series analysis reveals that the research paradigm in this field has evolved from single exercise methods to comprehensive exercise prescription studies, and multi-dimensional intervention studies combining exercise, diet, and pharmacological interventions are emerging as new research frontiers. Conclusions: This study uses bibliometric methods to visualize and analyze the progress of AE in T2DM intervention research from a broader perspective, providing a scientific overview and macro-level predictions for the research landscape in this field.