Peripheral nerve injuries often lead to permanent functional deficits, and current surgical or grafting techniques offer only partial recovery. Conductive hydrogels have recently emerged as a versatile platform that integrates tissue-like softness with electrical conductivity to actively promote nerve regeneration. By providing both mechanical support and electroactive cues, these materials enhance axonal extension, Schwann cell function, and neuroimmune modulation. Advances in hydrogel design-such as self-healing networks, injectability, and controlled release-further expand their therapeutic potential. Incorporating conductive polymers, nanomaterials, or ion-based systems enables precise tuning of conductivity and biological interactions. Preclinical studies demonstrate accelerated nerve repair and functional restoration, highlighting conductive hydrogels as a promising interface between biology and bioelectronics. Nonetheless, critical challenges remain, including long-term biocompatibility, controlled degradation, and scalable manufacturing for clinical translation. This review summarizes current design strategies, mechanisms, critically identifies evidence-based design principles most relevant for near-term clinical translation, while distinguishing speculative bioelectronic concepts from validated strategies.

Silicosis is a progressive and irreversible fibrotic lung disease resulting from chronic inhalation of crystalline silica (CS), for which no specific targeted therapy is clinically available. Thus, novel therapeutic agents and their molecular targets are urgently needed. Using GEO-based differential expression analysis and cMap drug prediction, this study identified capsazepine (CPZ) as a potential anti-silicosis agent. In vivo, CPZ dose-dependently ameliorated pulmonary dysfunction, reduced inflammatory cell infiltration and pro-inflammatory cytokine release, and suppressed collagen deposition and epithelial-mesenchymal transition (EMT) in lung tissues of silicosis model mice. In vitro, CPZ directly countered CS-induced inflammatory activation, apoptosis, and oxidative stress in macrophages, while inhibiting aberrant migration and fibrotic activation in fibroblasts, confirming its dual anti-inflammatory and anti-fibrotic effects at the cellular level. Mechanistically, CPZ bound to TRPV1 and subsequently blocked aberrant phosphorylation of the PI3K/AKT signaling pathway, thereby delaying silicosis progression. Collectively, this study is the first to demonstrate that CPZ is a candidate anti-silicosis drug with clinical translational potential, offering a new theoretical and experimental basis for targeted silicosis therapy.

Early in the pathogenesis of pulmonary fibrosis (PF), there are multiple inflammatory cell infiltrations in the damaged lung tissue. When lung injury persists, inflammatory cytokines prompt local fibroblasts migration and hyperproliferation, triggering abnormal deposition of extracellular matrix in the lung interstitium. This excessive repair leads to interstitial cell reorganization, triggering lung tissue fibrosis and further activation of inflammatory cells. Therefore, modulation of inflammatory mediators is of great significance in the treatment and prevention in the process of fibrosis. Cortex Mori Radicis (CMR) is a traditional Chinese herb with anti-inflammatory and antifibrotic properties. In this study, we investigated the therapeutic effects of CMR on bleomycin-induced PF using in vivo and in vitro models. In vivo experiments showed that CMR treatment significantly reduced inflammation, attenuated fibrosis, and alleviated lung function decline. In vitro, CMR inhibited migration, proliferation, and epithelial-mesenchymal transition (EMT) in A549 lung epithelial cells. Network pharmacological analysis identified 25 bioactive components and 10 key therapeutic targets in CMR, with the PI3K/AKT signaling pathway emerging as the core regulatory mechanism. Subsequent in vivo validation confirmed that CMR could inhibit the activation of the PI3K/AKT pathway. In conclusion, CMR exerts protective effects against PF by modulating the PI3K/AKT pathway, thereby attenuating inflammation and fibrotic remodeling. This study provides both pharmacodynamic evidence and mechanistic insight supporting the clinical potential of CMR and underscores the advantages of multitargeted intervention strategies offered by traditional Chinese medicine in the treatment of PF.

BackgroundSilicosis is a fatal form of pulmonary fibrosis caused by the inhalation of silica dust. Although the underlying pathogenesis remains unclear, and the macrophage-mediated immune response plays a central role in its development.ObjectiveTo investigate the expression, functional role, and upstream regulatory mechanism of C-C motif chemokine ligand 22 (CCL22) in silica-induced pulmonary fibrosis.MethodsThrough bioinformatics analysis, we identified CCL22 as a potential key factor in pulmonary fibrosis. We established in vitro models by stimulating human monocytic leukemia cells (THP-1) and peripheral blood mononuclear cell-derived macrophages (PBMC-m) with crystalline silica (CS). The regulation of CCL22 expression by CS was validated using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Subsequently, a conditioned co-culture system comprising macrophages and lung epithelial cells (BEAS-2B) was developed to evaluate the effects of CCL22 on lung epithelial cell function. Furthermore, the molecular mechanisms underlying CS-induced CCL22 secretion by macrophages were investigated using bioinformatics analysis, Western blot, specific inhibitors, qRT-PCR, and ELISA.ResultsBioinformatics analysis identified CCL22 as a key upregulated molecule in pulmonary fibrosis. In vitro experiments confirmed that CS treatment significantly enhanced CCL22 mRNA transcription and protein secretion in THP-1 and PBMC-m cells (P<0. 0001). In the co-culture system, supernatant from CS-stimulated macrophages with stable CCL22 knockdown significantly inhibited the scratch-healing ability and fibrotic process of BEAS-2B cells, and reversed the epithelial-mesenchymal transition (EMT) phenotype compared to the control group. Mechanism studies found that, compared to other transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB), the inhibition of of specific protein 1 (SP1) most significantly attenuated the CS-induced upregulation of CCL22. Furthermore, pathway inhibition experiments demonstrated that inhibiting extracellular signal-regulated kinase (ERK) reduced both CCL22 expression and p-SP1. Conversely, SP1 intervention did not affect ERK activation. ConclusionCS promotes CCL22 secretion by macrophages through the Raf/ERK-Sp1 signaling pathway, thereby driving fibrotic changes in pulmonary epithelial cells.

Epithelial-mesenchymal transition (EMT) is a key driver of idiopathic pulmonary fibrosis (IPF), yet therapies specifically targeting epithelial cells remain limited. The role of phosphodiesterase 7A (PDE7A) in IPF and its mechanism in regulating EMT are still largely unknown. This study aims to investigate the anti-fibrotic effect of BRL-50481, focusing on its target PDE7A and the associated molecular mechanism in regulating epithelial cell fibrosis and EMT. BRL-50481 was identified as a top candidate compound targeting pathogenic alveolar epithelial cells through bioinformatic screening. Its efficacy was evaluated in both a bleomycin-induced murine pulmonary fibrosis model and a TGF-β-induced A549 cell model. Drug-target interaction was characterized using molecular docking, cellular thermal shift assay (CETSA), and site-directed mutagenesis. Downstream signaling pathways were predicted via the TRRUST database and experimentally validated. PDE7A was found to be highly expressed in alveolar epithelial cells of IPF patients and mice. BRL-50481 directly bound to the ILE323 residue of PDE7A, specifically inhibiting JAK2/STAT3 signaling pathway activation. This inhibition suppressed EMT, inflammatory factor release, and collagen deposition, ultimately alleviating pulmonary fibrosis in both in vivo and in vitro models. PDE7A acts as a key upstream regulator driving JAK2/STAT3 signaling activation and the EMT process in alveolar epithelial cells. BRL-50481 exerts anti-fibrotic effects by precisely targeting this mechanism, providing novel insights into IPF pathogenesis and establishing a theoretical foundation for developing innovative therapies targeting PDE7A.

Silicosis, a debilitating occupational lung fibrosis caused by chronic silica dust inhalation, currently lacks effective therapeutic interventions, and its underlying molecular pathogenesis remains incompletely understood. To address this critical gap, we employed an integrated strategy combining bioinformatics, network pharmacology, and experimental validation to systematically identify novel therapeutic targets and candidate compounds for silicosis. Through analysis of silicosis-related differentially expressed genes from the GEO database and in silico prediction using the cMap platform, we identified the natural product chaetocin as a promising candidate. In a murine model of silicosis, chaetocin administration significantly improved pulmonary function and alleviated lung inflammation and collagen deposition. Notably, at a dose of 1 mg/kg, chaetocin demonstrated superior efficacy to pirfenidone, a current standard-of-care agent. In vitro studies further confirmed that chaetocin effectively attenuated silica-triggered macrophage inflammatory responses, apoptosis, and reactive oxygen species (ROS) production, while also suppressing fibroblast migration and activation. Mechanistic investigations revealed that chaetocin exerts its anti-inflammatory and anti-fibrotic effects by directly targeting HIF1α, thereby inhibiting the downstream PI3K/AKT/MMP9 signaling axis. Collectively, our findings establish chaetocin as a novel naturally-derived therapeutic candidate with significant potential for the treatment of silicosis.

Silicosis, formerly known as silico, is an irreversible disease caused by prolonged inhalation of substantial amounts of free crystalline silica dust, characterized by pulmonary inflammation and extensive nodular fibrosis. The etiology of the disease remains unclear, which currently hinders the development of effective therapeutic drugs and interventions. Ingenol (Ing), a terpenoid active ingredient found in plants of the Euphorbiaceae family, including the entire herb of Euphorbia helioscopia, Euphorbia kansui, or Euphorbia lathyris, demonstrates significant anti-inflammatory and antiviral activities. In this study, we identified and confirmed that Ingenol can significantly ameliorate silicosis induced by silica dioxide by inhibiting the PTGS2/PI3K/AKT signaling pathway. In vivo, Ingenol improves pulmonary respiratory function and reduces inflammation and fibrosis in a murine model of CS-induced silicosis. In vitro, Ingenol inhibits the expression of cellular factors associated with inflammation and fibrosis, as well as macrophage apoptosis and fibroblast migration. Furthermore, it can modulate the expression of fibrosis-related proteins, thereby inhibiting CS-induced fibrotic responses. Mechanistically, a combination of bioinformatics, network pharmacology, and experimental validation indicates that Ingenol mitigates the progression of silicosis by modulating the PTGS2/PI3K/AKT signaling pathway. In summary, these findings suggest that Ingenol is a potential candidate for the treatment of silicosis.

The development of lung adenocarcinoma (LUAD) is intricately linked with cell cycle regulation and epithelial-mesenchymal transition (EMT). Our study, leveraging bioinformatics and database analysis, identified FUCA2 as a key gene influencing the prognosis and progression of LUAD. We observed that FUCA2 is highly expressed in LUAD and correlates with poor outcomes. Functionally, we assessed the role of this gene through cell cloning, scratch assays, transwell migration, and western blotting, revealing that FUCA2 knockdown significantly inhibits tumor cell proliferation and migration, downregulates the expression of cell cycle and EMT-related proteins, and markedly reduces tumor burden. Mechanistically, pathway enrichment analysis identified GGH as a downstream target of FUCA2. Knockdown of GGH similarly inhibits the proliferation, migration, and cell cycle progression of LUAD cells. FUCA2 upregulates GGH to modulate cell cycle and EMT in LUAD. Collectively, our findings indicate that the FUCA2/GGH axis promotes LUAD progression by regulating cell cycle and EMT.

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disorder with limited effective therapeutic options. In this study, differential gene expression analysis of lung tissues from IPF patients and alveolar type 2 (AT2) cells identified BI-2536 as a potential therapeutic candidate for IPF. In an in vivo model, BI-2536 significantly ameliorated bleomycin (BLM)-induced pulmonary function decline in IPF mice while suppressing pulmonary inflammation and fibrosis markers, thereby mitigating pathological lung tissue damage. Further investigations revealed that polo-like kinase 2 (PLK2) serves as a key target of BI-2536, with Gly92 identified as a critical binding residue. Mechanistically, BI-2536 binds to PLK2, inhibiting downstream phosphorylation of JNK1/2 and SP1, consequently suppressing BLM-induced epithelial-mesenchymal transition (EMT) and fibrotic progression in AT2 cells. In summary, this study demonstrates that BI-2536 delays IPF progression by inhibiting the PLK2/JNK/SP1 signaling pathway in AT2 cells, providing a novel therapeutic agent and target for pulmonary fibrosis treatment.

OBJECTIVE:Herein, we employed a novel integrated radiomics and transcriptomics approach to identify key biomarkers for pneumoconiosis. Specifically, we combined thoracic Computed Tomography (CT) imaging-based phenomics and peripheral blood gene expression analysis to improve early diagnosis and risk stratification of pneumoconiosis. METHODS:The study cohort comprised individuals with diagnosed pneumoconiosis and healthy coal miners. Participants were categorized into low-, medium-, and high-risk groups, as well as a pneumoconiosis group, based on radiomics scoring. Peripheral blood samples were collected for transcriptome sequencing analysis, and key genes were selected through differential expression and trend analysis. Mfuzz clustering analysis and KEGG pathway enrichment analysis were utilized to further investigate gene expression patterns and functions. The expression of key genes was verified using real-time quantitative PCR and western blotting. The diagnostic value of key genes was assessed using Receiver Operating Characteristic (ROC) analysis. A mouse model was constructed to assess the role of TFCP2 in pneumoconiosis and to explore its potential mechanisms. RESULTS:Our findings revealed that heterogeneous gene expression patterns correlated with an increased pneumoconiosis risk. Additionally, TFCP2 emerged as a significant biomarker (AUC = 0.799), with its expression levels increasing with pneumoconiosis risk. Furthermore, TFCP2 upregulation correlated closely with Extracellular Matrix (ECM)-receptor interactions and AGE-RAGE signaling pathways, which have been associated with fibrosis and inflammatory responses in lung tissue. Moreover, silencing TFCP2 in a mouse model improved silica-induced pulmonary fibrosis, with USP22 identified as a downstream target gene of TFCP2. CONCLUSION:TFCP2 may serve as a potential biomarker and therapeutic target for the progression of pneumoconiosis. Its high expression in lung epithelial cells may exacerbate pulmonary fibrosis by promoting EMT and ECM deposition. This study provides new molecular targets for the early diagnosis and treatment of pneumoconiosis.

Silicosis, a pervasive and life-threatening occupational respiratory disease, poses a substantial global health burden, particularly affecting those in impacted communities and their families. Characterized by irreversible pulmonary fibrosis, the disease's complex pathogenesis remains poorly elucidated, presenting significant challenges for therapeutic intervention. This study integrates bioinformatics, network pharmacology, and experimental validation to explore the potential mechanisms and therapeutic drugs for silicosis. Initially, differentially expressed genes (DEGs) in silicosis were subjected to GO and KEGG pathway enrichment analysis. Subsequently, the DEGs were imported into the cMap database for drug prediction, leading to the identification of piperine (PIP) as a candidate drug for the treatment of silicosis. Network pharmacology analysis then determined the pharmacological targets of PIP and demonstrated its ability to modulate the JAK2-STAT3 signaling pathway. Finally, we validated the therapeutic effects and mechanisms of PIP in silicosis. In vivo, PIP significantly ameliorated inflammation and fibrosis induced by crystalline silica (CS) in a murine model of silicosis, including inflammatory cell infiltration, formation of inflammasomes, deposition of collagen fibers and extracellular matrix, and expression of inflammatory and fibrotic factors. In vitro, PIP inhibited CS-induced cytokine expression, ROS generation, macrophage apoptosis, and activation of the JAK2-STAT3 signaling pathways. Collectively, our research identifies and validates PIP as a promising candidate for the improvement of silicosis.

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.

PRDX2 is significantly expressed in various cancers and is associated with the proliferation of tumor cells. Nonetheless, the precise mechanism of PRDX2 in tumor immunity remains incompletely understood. This study aims to investigate the impact of PRDX2, which is highly expressed in lung adenocarcinoma, on T cells in the tumor immune microenvironment, and its immune action target to promote the immune escape of lung cancer cells, to provide a theoretical basis for lung adenocarcinoma treatment with PRDX2 as the target. Mouse animal models to verify the effect of Conoidin A treatment on tumor growth and T cell infiltration. Flow cytometry and Western blot verified tumor cell apoptosis in the in vitro co-culture system as well as granzyme B and perforin expression in T cells. RNA-Seq was used to obtain the downstream immune molecule. si-RNA knockdown of Galectin-9 was co-cultured with T cells in vitro. Immunofluorescence and Western blot verified that PRDX2 regulates Galectin-9 expression through HDAC3. PRDX2 expression was negatively correlated with CD8+ T cell expression in LUAD patients. Inhibition of PRDX2 significantly enhanced T-cell killing of LUAD cells and reduced tumor load in both in vitro and in vivo models. Mechanistically, Conoidin A or shRNA_PRDX2 decreased Galectin-9 expression by down-regulating the phosphorylation of HDAC3, consequently enhancing the infiltration and function of CD8+ T cells. This study reveals the role of the PRDX2/HDAC3/Galectin-9 axis in LUAD immune escape and indicates Galectin-9 as a promising target for immunotherapy.

Phosphatase and tensin homolog (PTEN) is a critical inhibitor of the PI3K/AKT signaling pathway, yet its direct upstream regulators remain poorly defined. In this study, we investigated the role of peroxiredoxin 4 (PRDX4) in alveolar macrophages (AMs) activation and pulmonary fibrosis. Analyses of lung tissues from silicosis patients by transcriptomic and histological analyses revealed that PRDX4 is selectively upregulated in AMs and positively correlated with profibrotic and inflammatory gene expression. Consistent results were observed in silicosis model mice, where PRDX4 expression co-localized with the macrophage marker F4/80 and correlated with fibrotic indicators. Functional studies demonstrated that macrophage-specific silencing of PRDX4 using adeno-associated virus improved lung function and reduced inflammatory infiltration and fibrosis. PRDX4 upregulation aberrantly activated AMs and promoted epithelial–mesenchymal transition and fibroblast–myofibroblast transition. Mechanistically, PRDX4 enhanced AKT/NF-κB signaling with minimal effects on PI3K. Biochemical interaction assays further demonstrated that oligomeric PRDX4 disrupted PTEN homodimer formation, with mutational analyses identifying Cys124 and Cys245 as essential residues. Notably, Conoidin A alleviated crystalline silica–induced fibrosis in mice, with its therapeutic effect likely mediated by disrupting PRDX4 oligomerization. These findings identify PRDX4 as a novel upstream regulator of PTEN, establish a mechanistic PRDX4–PTEN axis in macrophage activation, and highlight PRDX4 as a promising therapeutic target for idiopathic pulmonary fibrosis and silicosis-associated fibrosis.

BACKGROUND:Triple-negative breast cancer (TNBC) is characterized by high invasiveness, high potential for metastasis, easy recurrence, and poor prognosis. There is an urgent need to develop new clinical treatments. METHODS:This study utilized TNBC tissue microarrays to detect Peroxiredoxin 2 (PRDX2) expression levels and analyzed the correlation between PRDX2 and tumor invasion as well as invasion-related gene expression through the TCGA database. A stable PRDX2-knockdown triple-negative breast cancer cell line was established using lentiviral technology. The effects of PRDX2 on triple-negative breast cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) were investigated via wound healing assays, Transwell assays, qPCR, and Western blotting. RNA sequencing (RNA-seq), Western blotting, and dual luciferase reporter assays were performed to confirm that PRDX2 regulates FN1 expression through SP1. Furthermore, subcutaneous tumor xenograft models in nude mice were constructed to assess the effects of PRDX2 knockdown and the PRDX2 inhibitor Conoidin A on tumor growth in vivo. RESULTS:Tissue microarray detection and correlative analysis revealed that PRDX2 is significantly upregulated in triple-negative breast cancer (TNBC) tumor tissues and positively correlated with genes associated with cell migration and invasion. Functional experiments demonstrated that in vitro knockdown of PRDX2 suppresses migration, invasion, and epithelial-mesenchymal transition (EMT) in TNBC cells. Furthermore, in vivo knockdown of PRDX2 or treatment with the PRDX2 inhibitor Conoidin A effectively reduced tumor burden. Mechanistic investigations utilizing RNA sequencing (RNA-seq) identified FN1 as a critical gene promoting TNBC cell migration and invasion. PRDX2 facilitates TNBC progression by activating the PI3K/AKT signaling pathway, which enhances SP1 binding to the FN1 gene promoter. This regulatory cascade ultimately drives tumor advancement in TNBC. CONCLUSIONS:This study elucidates the role of the PRDX2/SP1/FN1 axis in TNBC migration and invasion, and highlights PRDX2 as a promising therapeutic target for triple-negative breast cancer.

Lung adenocarcinoma (LUAD), as a prevalent and life-threatening malignancy, poses a significant global health burden, particularly impacting patients and their families profoundly. Peroxiredoxin-2 (PRDX2) exhibits high expression levels in LUAD tissues. However, the identification of efficient and low-toxicity small-molecule inhibitors targeting PRDX2 from traditional Chinese medicine remains a challenging task. This study aims to identify potential inhibitors of PRDX2 in lung adenocarcinoma and elucidate their mechanism of action. Molecular docking and thermal shift assays were employed to evaluate the interaction between luteolin and PRDX2 protein. The effects of luteolin on lung cancer cell behavior were assessed through in vitro cellular experiments, and its efficacy on tumor growth was validated in a mouse model. Additionally, flow cytometry and Western blot analysis were utilized to investigate the mechanism of luteolin's action. Molecular docking and thermal shift experiments confirmed the binding affinity of luteolin to PRDX2. In vitro experiments demonstrated that luteolin significantly inhibits the proliferation and migration of LUAD cells. In vivo experiments showed that luteolin effectively suppresses tumor growth in an immunocompetent lung cancer mouse model. Western blot results untangled that luteolin promotes apoptosis of lung cancer cells by enhancing T-cell-mediated killing pathways via PRDX2. In summary, luteolin binds to PRDX2, inhibiting the JAK2/STAT3 pathway, suppressing PD-L1 expression, promoting the release of perforin and granzyme B from CD8+ T cells, and inhibiting immune evasion in LUAD, thereby inhibiting the progression of lung adenocarcinoma.

The adenosine-signaling axis has been recognized as an important immunomodulatory pathway in tumor immunity. However, the biological role of the adenosine-signaling axis in the remodeling of the tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unclear. Here, we quantified adenosine signaling (ado_sig) in LUAD samples using the GSVA method and assessed the prognostic value of adenosine in LUAD. Afterward, we explored the heterogeneity of the tumor-immune microenvironment at different adenosine levels. In addition, we analyzed the potential biological pathways engaged by adenosine. Next, we established single-cell transcriptional profiles of LUAD and analyzed cellular composition and cell-cell communication analysis under different adenosine microenvironments. Moreover, we established adenosine-related prognostic signatures (ARS) based on comprehensive bioinformatics analysis and evaluated the efficacy of ARS in predicting immunotherapy. The results demonstrated that adenosine signaling adversely impacted the survival of immune-enriched LUAD. The high-adenosine microenvironment exhibited elevated pro-tumor-immune infiltration, including M2 macrophages and displayed notably increased epithelial-mesenchymal transition (EMT) transformation. Furthermore, adenosine signaling displayed significant associations with the expression patterns and prognostic value of immunomodulators within the TME. Single-cell sequencing data revealed increased fibroblast occupancy and a prominent activation of the SPP1 signaling pathway in the high adenosine-signaling microenvironment. The ARS exhibited promising effectiveness in prognostication and predicting immunotherapy response in LUAD. In summary, overexpression of adenosine can cause a worsened prognosis in the LUAD with abundant immune infiltration. Moreover, increased adenosine levels are associated with pro-tumor-immune infiltration, active EMT transformation, pro-tumor angiogenesis, and other factors promoting cancer progression, which collectively contribute to the formation of an immunosuppressive microenvironment. Importantly, the ARS developed in this study demonstrate high efficacy in evaluating the response to immunotherapy.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease characterized by severe pulmonary fibrosis, for which there is an urgent need for effective therapeutic agents. Mefloquine (Mef) is a quinoline compound primarily used for the treatment of malaria. However, high doses (>25 mg/kg) may lead to side effects such as cardiotoxicity and psychiatric disorders. Here, we found that low-dose Mef (5 mg/kg) can safely and effectively treat IPF mice. Functionally, Mef can improve the pulmonary function of IPF mice (PIF, PEF, EF50, VT, MV, PENH), alleviating pulmonary inflammation and fibrosis by inhibiting macrophage activity. Mechanically, Mef probably regulates the Jak2/Stat3 signaling pathway by binding to the 492HIS site of Potassium voltage-gated channel subfamily H member 2 (KCNH2) protein in macrophages, inhibiting the secretion of macrophage inflammatory and fibrotic factors. In summary, Mef may inhibit macrophage activity by binding to KCNH2 protein, thereby slowing down the progress of IPF.

Objection Investigating the key genes and mechanisms that influence stemness in lung adenocarcinoma. Methods First, consistent clustering analysis was performed on lung adenocarcinoma patients using stemness scoring to classify them. Subsequently, WGCNA was utilized to identify key modules and hub genes. Then, machine learning methods were employed to screen and identify the key genes within these modules. Lastly, functional analysis of the key genes was conducted through cell scratch assays, colony formation assays, transwell migration assays, flow cytometry cell cycle analysis, and xenograft tumor models. Results First, two groups of patients with different stemness scores were obtained, where the high stemness score group exhibited poor prognosis and immunotherapy efficacy. Next, LASSO regression analysis and random forest regression were employed to identify genes (PBK, RACGAP1) associated with high stemness scores. RACGAP1 was significantly upregulated in the high stemness score group of lung adenocarcinoma and closely correlated with clinical pathological features, poor overall survival (OS), recurrence-free survival (RFS), and unfavorable prognosis in lung adenocarcinoma patients. Knockdown of RACGAP1 suppressed the migration, proliferation, and tumor growth of cancer cells. Conclusion RACGAP1 not only indicates poor prognosis and limited immunotherapy benefits but also serves as a potential targeted biomarker influencing tumor stemness.

Artesunate holds excellent promise for lung cancer treatment, but its target is still unclear. We used molecular docking techniques to predict artesunate and Fatty acid binding protein 5 (FABP5) binding sites. Cellular thermal shift assay (CETSA) verified that artesunate treatment could promote the stability of the FABP5 protein. There was no significant change in the strength of the FABP5 protein after the mutation of binding sites by adding artesunate treatment. Mechanistically, artesunate promotes apoptosis in lung cancer cells by binding to FABP5, inhibiting the expression of the lipid metabolism gene SCD, and suppressing the expression of the SCD transcription factor regulated by the transcription factor PPARγ. In summary, our study shows that the protein targeted by artesunate is FABP5 and that artesunate promotes apoptosis through the FABP5-PPARγ-SCD pathway, which offers excellent potential for treating lung cancer.