Eosinophil-associated diseases are a group of inflammatory disorders characterized by abnormal eosinophil infiltration, which significantly impacts patients’ quality of life. Interleukin-5 (IL-5), a critical cytokine that regulates eosinophil development, activation, chemotaxis, and survival, plays a central role in the pathogenesis of these diseases. This review systematically examines the molecular structure and signaling pathways of IL-5, its mechanisms of action in asthma and chronic obstructive pulmonary disease (COPD), and the development and clinical applications of monoclonal antibodies (e.g., mepolizumab, benralizumab, reslizumab) and other biologics targeting IL-5. Although IL-5-targeted therapies have yielded significant results, single-target interventions still exhibit limitations, including insufficient responses in certain patients. To address this, we explore the strategy of multi-target combination therapies, such as the synergistic inhibition of IL-5 with the IL-4/IL-13 and IL-33/ST2 pathways. We also discuss the potential of novel therapeutic approaches, including bispecific antibodies and small-molecule inhibitors. Ultimately, multi-targeted precision therapies, tailored to individual inflammatory phenotypes, are anticipated to represent a new frontier in the management of eosinophil-associated diseases.

This review elucidates the pivotal role of alveolar type II epithelial cells (AT2) as key adult stem cells in lung homeostasis maintenance and post-injury repair, with molecular regulatory mechanisms. We synthesize current knowledge on AT2 self-renewal and differentiation into alveolar type I epithelial cells (AT1), and how their dysfunction drives refractory lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. By evaluating findings from lineage tracing, single-cell transcriptomics, and three-dimensional organoid culture, this article outlines the cellular atlas of alveolar regeneration. This atlas encompasses not only AT2 cells and alveolar epithelial progenitors, but also auxiliary progenitor sources such as bronchioalveolar stem cells and lineage-negative epithelial progenitors. Notably, the review highlights the transitional plasticity stage—alveolar differentiation intermediate states—during AT2-to-AT1 differentiation. Mechanistically, the review delves into the intricate signaling networks governing AT2 cell fate, including key pathways such as Wnt/β-catenin, Hippo-YAP, Notch, and BMP. Crucially, it emphasizes that AT2 cell regenerative capacity relies on a multilayered quality control system involving epigenetic regulation, metabolic reprogramming, organelle homeostasis, and telomere maintenance. Furthermore, mesenchymal and immune cells within the alveolar stem cell niche engage in precise paracrine crosstalk with AT2 cells to collectively orchestrate regeneration. Finally, this review bridges fundamental biological discoveries with clinical prospects, illustrating how AT2 cells may serve as biomarkers for disease diagnosis, vehicles for gene-targeted therapy, and sources for cell replacement therapy. It outlooks novel treatments by modulating AT2 stem cell function—including small-molecule drugs, gene-editing nanoplatforms, and stem cell transplantation—heralding a transformative era in pulmonary regenerative medicine. Graphical Abstract

Atopic dermatitis ( ad ) is a chronic inflammatory skin disease, with recent studies indicating that immune cells, such as monocytes and inflammatory cytokines, play a crucial role. By retrieving datasets from public databases and analysing immune cell infiltration in lesional skin using CIBERSORT, we found that monocytes and M2 macrophages were significantly upregulated in atopic dermatitis. Differentially expressed gene (DEG) functional enrichment analysis revealed that cytokine‐cytokine receptor interaction was the most significantly enriched pathway. Further analysis of cytokines and their receptors, along with their correlation with infiltrating immune cells, identified IL36G‐expressing monocytes as a key target in atopic dermatitis. We compared immune cell infiltration and cytokine‐related targets in similar inflammatory skin diseases, such as psoriasis and urticaria, to evaluate similarities and differences among these three skin conditions. The analysis revealed that IL36G‐expressing monocytes were also highly expressed in psoriasis but did not play a pivotal role in urticaria. Finally, we used molecular docking to predict and validate drugs targeting IL36G. Our study highlights IL36G‐expressing monocytes as a common key target in atopic dermatitis and psoriasis, offering novel insights and therapeutic strategies for these related diseases.

Network pharmacology and molecular docking are widely applied in drug discovery, yet fragmented workflows and inconsistent operations frequently undermine result reproducibility. Here, a standardized protocol integrating these approaches into a reproducible framework for drug screening and mechanism exploration is described, with the workflow organized into three sequential phases: data preparation, computational analysis, and validation. In the preparation phase, compound libraries from public databases are filtered via Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) criteria, including oral bioavailability, drug-likeness, and toxicity prediction, while potential therapeutic targets are obtained through target prediction and integration of disease-related databases to comprehensively identify drug-disease interaction candidates. In the computational analysis phase, overlapping targets undergo Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and protein-protein interaction network topological analysis to identify core targets; molecular docking is configured with two standardized optional strategies with distinct advantages. The two-step progressive strategy employs AutoDock Vina for high-throughput preliminary screening of the compound library, followed by precise re-docking with YASARA, which eliminates false positives from high-throughput screening and generates protein-ligand complexes natively compatible with subsequent YASARA molecular dynamics (MD) simulations to avoid structural deviations caused by cross-software format conversion. The one-step strategy completes the full docking process via YASARA alone, which simplifies the operation workflow, improves experimental efficiency, and is fully applicable for specific research goals. In the validation phase, standardized MD simulations evaluate ligand-protein complex stability via core metrics of root mean square deviation (RMSD) and root mean square fluctuation (RMSF). This unified, reproducible pipeline enhances the reliability of network pharmacology and docking studies and facilitates cross-study comparisons in computational drug discovery.