Hua Ye

Introduction: Yifei Capsule (YFC), a Traditional Chinese Medicine (TCM) formulation, has shown clinical benefit in patients with stable Chronic Obstructive Pulmonary Disease (COPD). However, its molecular mechanisms remain insufficiently understood. This study aimed to systematically investigate the active compounds, key targets, and signaling pathways underlying the therapeutic effects of YFC in stable COPD by integrating computational pharmacology with single-cell transcriptomic validation. Methods: An integrated workflow combining network pharmacology, molecular docking, and 100 ns Molecular Dynamics (MD) simulations was used to identify bioactive compounds, candidate therapeutic targets, and major signaling pathways of YFC. To externally validate the in silico findings, an independent public single-cell RNA sequencing (scRNA-seq) dataset (GSE249584) containing 54,821 cells from 15 human samples (7 controls and 8 COPD patients) was analyzed to characterize the cell-type-specific expression patterns of hub genes in COPD. Results: A total of 167 bioactive compounds in YFC and 977 putative targets were identified, of which 222 overlapped with COPD-related targets. Network topology analysis identified SRC, PIK3R1, and STAT3 as major hub genes, and KEGG enrichment analysis indicated that these targets were primarily enriched in the PI3K-Akt signaling pathway (hsa04151, p = 1.23E-15). Molecular docking revealed strong binding affinities between representative compounds and core targets, while MD simulations confirmed the dynamic stability of key complexes, particularly SRC-Korseveriline. scRNA-seq analysis further demonstrated cell-type-specific dysregulation of hub genes in COPD: STAT3 was significantly upregulated in monocyte/macrophage populations (adjusted p = 6.59E-08, log2FC = 0.32), PIK3R1 was downregulated in T cells (adjusted p = 2.05E-20, log2FC = -0.41), and SRC showed bimodal expression, with upregulation in endothelial cells (adjusted p = 0.002, log2FC = 0.38) but downregulation in T cells (adjusted p = 0.03, log2FC = -0.27). Discussion: These findings suggest that YFC may exert therapeutic effects in stable COPD through multi-component, multi-target regulation of the PI3K-Akt pathway and related inflammatory signaling networks. The cell-type-specific dysregulation of SRC, PIK3R1, and STAT3 supports a nuanced immunomodulatory and vascular-regulatory mechanism, highlighting the value of integrating computational prediction with single-cell transcriptomic evidence. Conclusion: This multi-scale study provides a mechanistic framework for understanding the action of YFC in stable COPD and identifies SRC, PIK3R1, and STAT3 as plausible core targets. The results support the utility of combining network pharmacology, molecular simulation, and single-cell transcriptomics to dissect the mechanisms of complex herbal medicines. Nevertheless, the present findings remain correlative and require further experimental validation to establish causality.

Background: The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent. Objectives: This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action. Methods: This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the ‘MR-PRESSO’ package and ‘Mendelian Randomization’ package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure. Results: Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation. Conclusions: The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms through which Omega-3 prevents ischemic stroke. In summary, incorporating an increased intake of Omega-3 in the diet can serve as one of the dietary intervention strategies for patients with hypertension. Additionally, it can act as an adjunctive therapy for the prevention of ischemic strokes and their complications.

Various techniques such as data mining, network pharmacology, molecular docking and molecular dynamics simulation were used in this study to screen and validate effective herbal medicines for the treatment of idiopathic pulmonary fibrosis (IPF) and to reveal their mechanisms of action at the molecular level. The use of this approach will provide new tools and ideas for future drug screening, especially for the application of herbal medicines in the treatment of complex diseases. Among them, the five identified core targets, including IL6, TP53, AKT1, VEGFA, and TNF, as well as a series of major active compounds, will be important references for future anti-IPF drug development. This information will accelerate the discovery and development of relevant drugs. Meanwhile, this study further confirmed the potential value of four Chinese herbal medicines, including Gancao, Danshen, Huangqin, and Sanqi, in the treatment of IPF. This will promote more clinical trials and practices to confirm and optimise the application of these herbs. Finally, this study is an important theoretical guide to enhance the advantages of Chinese herbal medicines in the prevention and treatment of major and difficult diseases, as well as to understand and utilise the potential efficacy of Chinese herbal medicines. This will further promote the scientific research and clinical application of herbal medicines and provide more possibilities for future disease treatmentCommunicated by Ramaswamy H. Sarma

Supersaturation is a promising strategy to improve gastrointestinal absorption of poorly water-soluble drugs. Supersaturation is a metastable state and therefore dissolved drugs often quickly precipitate again. Precipitation inhibitors can prolong the metastable state. Supersaturating drug delivery systems (SDDS) are commonly formulated with precipitation inhibitors, hence the supersaturation is effectively prolonged for absorption, leading to improved bioavailability. This review summarizes the theory of and systemic insight into supersaturation, with the emphasis on biopharmaceutical aspects. Supersaturation research has developed from the generation of supersaturation (pH-shift, prodrug and SDDS) and the inhibition of precipitation (the mechanism of precipitation, the character of precipitation inhibitors and screening precipitation inhibitors). Then, the evaluation approaches to SDDS are discussed, including in vitro, in vivo and in silico studies and in vitro–in vivo correlations. In vitro aspects involve biorelevant medium, biomimetic apparatus and characterization instruments; in vivo aspects involve oral absorption, intestinal perfusion and intestinal content aspiration and in silico aspects involve molecular dynamics simulation and pharmacokinetic simulation. More physiological data of in vitro studies should be taken into account to simulate the in vivo environment. The supersaturation theory should be further completed, especially with regard to physiological conditions.

Increasing interest is aroused by traditional Chinese medicine (TCM) treatment of chronic hepatitis B (CHB) based on specific TCM syndrome. As the most common CHB syndromes, spleen‐stomach dampness‐heat (SSDH) syndrome and liver‐gallbladder dampness‐heat (LGDH) syndrome are still apt to be confused in TCM diagnosis, greatly hindering the stable exertion of TCM effectiveness. It is urgently needed to provide objective and biological evidences for differentiation and identification of the two significant syndromes. In this study, microRNA (miRNA) microarray analyses coupled with bioinformatics were employed for comparative miRNA profiling of SSDH and LGDH patients. It was found that the two syndromes had both the same and different significantly differentially expressed miRNAs (SDE‐miRNAs). Commonness and specificity were also both found between their SDE‐miRNA‐based bioinformatics analyses, including Hierarchical Clustering, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and miRNA‐GO/pathway networks. Furthermore, syndrome‐specific SDE‐miRNAs were identified as the potential biomarkers, including hsa‐miR‐1273g‐3p and hsa‐miR‐4419b for SSDH as well as hsa‐miR‐129‐1‐3p and hsa‐miR‐129‐2‐3p for LGDH. All these laid biological and clinical bases for classification and diagnosis of the two significant CHB dampness‐heat syndromes including SSDH and LGDH, providing more opportunities for better application of TCM efficacy and superiority in CHB treatment.