Emerging delivery approaches for targeted pulmonary fibrosis treatment

Diwan, Rimpy; Bhatt, Himanshu N.; Beaven, Elfa; Nurunnabi, Md

doi:10.1016/j.addr.2023.115147

Cited by 16 publications

(1 citation statement)

References 423 publications

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“…Epithelial cell dysfunction is an important mechanism in the pathogenesis of IPF. Dysfunction leads to increased secretion of TGF-β signaling, promoting the activation of local fibroblasts and enhancing pro-fibrotic mechanisms away from the epithelium [ 9 , 10 , 11 ]. Specific biomarkers of epithelial dysfunction include mucin 5B (MUC5B), which exhibits elevated expression in terminal bronchi and honeycomb cysts.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Function and Immunologic Landscape of a Predictive Model Based on Five Senescence-Related Genes in IPF Bronchoalveolar Lavage Fluid

Zhong,

Lei,

Zhang

et al. 2024

Biomedicines

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Background: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by unknown causes and a poor prognosis. Recent research indicates that age-related mechanisms, such as cellular senescence, may play a role in the development of this condition. However, the relationship between cellular senescence and clinical outcomes in IPF remains uncertain. Methods: Data from the GSE70867 database were meticulously analyzed in this study. The research employed differential expression analysis, as well as univariate and multivariate Cox regression analysis, to pinpoint senescence-related genes (SRGs) linked to prognosis and construct a prognostic risk model. The model’s clinical relevance and its connection to potential biological processes were systematically assessed in training and testing datasets. Additionally, the expression location of prognosis-related SRGs was identified through immunohistochemical staining, and the correlation between SRGs and immune cell infiltration was deduced using the GSE28221 dataset. Result: The prognostic risk model was constructed based on five SRGs (cellular communication network factor 1, CYR61, stratifin, SFN, megakaryocyte-associated tyrosine kinase, MATK, C-X-C motif chemokine ligand 1, CXCL1, LIM domain, and actin binding 1, LIMA1). Both Kaplan-Meier (KM) curves (p = 0.005) and time-dependent receiver operating characteristic (ROC) analysis affirmed the predictive accuracy of this model in testing datasets, with respective areas under the ROC curve at 1-, 2-, and 3-years being 0.721, 0.802, and 0.739. Furthermore, qRT-RCR analysis and immunohistochemical staining verify the differential expression of SRGs in IPF samples and controls. Moreover, patients in the high-risk group contained higher infiltration levels of neutrophils, eosinophils, and M1 macrophages in BALF, which appeared to be independent indicators of poor prognosis in IPF patients. Conclusion: Our research reveals the effectiveness of the 5 SRGs model in BALF for risk stratification and prognosis prediction in IPF patients, providing new insights into the immune infiltration of IPF progression.

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Section: Introductionmentioning

confidence: 99%

Prognostic Function and Immunologic Landscape of a Predictive Model Based on Five Senescence-Related Genes in IPF Bronchoalveolar Lavage Fluid

Zhong,

Lei,

Zhang

et al. 2024

Biomedicines

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MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice

Jin,

Bao,

Huang

et al. 2024

Journal Cellular Physiology

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The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin‐induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor‐β1 (TGF‐β1)‐induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G‐protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.

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Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell‐Mediated Biomedical Applications

Zheng,

Tian,

et al. 2024

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Stem cell‐related therapeutic technologies have garnered significant attention of the research community for their multi‐faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell‐cell and cell‐matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell‐related research. Microfluidics offers an intriguing platform to produce stem cell‐laden hydrogel microparticles (SCHMs) owing to its ability to manipulate the fluids at the micrometer scale as well as precisely control the structure and composition of microparticles. In this review, the typical biomaterials and crosslinking methods for microfluidic encapsulation of stem cells as well as the progress in droplet‐based microfluidics for the fabrication of SCHMs are outlined. Moreover, the important biomedical applications of SCHMs are highlighted, including regenerative medicine, tissue engineering, scale‐up production of stem cells, and microenvironmental simulation for fundamental cell studies. Overall, microfluidics holds tremendous potential for enabling the production of diverse hydrogel microparticles and is worthy for various stem cell‐related biomedical applications.

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Emerging delivery approaches for targeted pulmonary fibrosis treatment

Cited by 16 publications

References 423 publications

Prognostic Function and Immunologic Landscape of a Predictive Model Based on Five Senescence-Related Genes in IPF Bronchoalveolar Lavage Fluid

Prognostic Function and Immunologic Landscape of a Predictive Model Based on Five Senescence-Related Genes in IPF Bronchoalveolar Lavage Fluid

MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice

Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell‐Mediated Biomedical Applications

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