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Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds to CD206 on M2-polarized bone marrow-derived macrophages (BMDM) in vitro, resulting in a time-dependent decrease in CD206 expression and a transient increase in M1-macrophage marker TNF-α. To elucidate the antifibrotic effects of RP-832c, we used a murine model of bleomycin (BLM)-induced early-stage pulmonary fibrosis. RP-832c significantly reduced fibrosis in a dose-dependent manner, and decreased CD206, TGF-β1, and α-SMA expression in mouse lungs. Similarly, in an established model of lung fibrosis, RP-832c significantly decreased lung fibrosis and significantly decreased inflammatory cytokines TNF-α, IL-6, IL-10, IFN-γ, CXCL1/2, and fibrosis markers TGF-β1 and MMP-13. In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Simple Summary: African American (AA) women with breast cancer are more likely to have higher inflammation and a stronger overall immune response than European American (EA) women. In this report, we demonstrate the biological role of Kaiso in the immune signaling of breast cancer exosomes. Our findings indicate that Kaiso directly represses tumor suppressor THBS1, and this is associated with increased expression of CD47 and signal regulatory protein (SIRPA). Kaiso depletion attenuated tumor formation in athymic nude mice, and this is associated with increased infiltration of M1 macrophages. In vitro studies using THP1 cells that were treated with exosomes from Kaiso-depleted cells polarize towards the M1 phenotype with increased phagocytosis of cancer cells compared to high Kaiso control exosome, which polarizes towards an M2 phenotype. In summary, these findings reveal that Kaiso modulates the macrophage-mediated immune escape of cancer cells through exosome signaling, which may be related to poorer outcomes, especially for AA women. African American (AA) women with breast cancer are more likely to have higher inflammation and a stronger overall immune response, which correlate with poorer outcomes. In this report, we applied the nanostring immune panel to identify differences in inflammatory and immune gene expression by race. We observed a higher expression of multiple cytokines in AA patients compared to EA patients, with high expression of CD47, TGFB1, and NFKB1 associated with the transcriptional repressor Kaiso. To investigate the mechanism associated with this expression pattern, we observed that Kaiso depletion results in decreased expression of CD47, and its ligand SIRPA. Furthermore, Kaiso appears to directly bind to the methylated sequences of the THBS1 promotor and repress gene expression. Similarly, Kaiso depletion attenuated tumor formation in athymic nude mice, and these Kaiso-depleted xenograft tissues showed significantly higher phagocytosis and increased infiltration of M1 macrophages. In vitro validation using MCF7 and THP1 macrophages treated with Kaiso-depleted exosomes showed a reduced expression of immune-related markers (CD47 and SIRPA) and macrophage polarization towards the M1 phenotype compared to MCF7 cells treated with exosomes isolated from high-Kaiso cells. Lastly, analysis of TCGA breast cancer patient data demonstrates that this gene signature is most prominent in the basal-like subtype, which is more frequently observed in AA breast cancer patients. [ABSTRACT FROM AUTHOR]

Hydrogels are polymeric materials widely used in medicine due to their similarity with the biological components of the body. Hydrogels are biocompatible materials that have the potential to promote cell proliferation and tissue support because of their hydrophilic nature, porous structure, and elastic mechanical properties. In this work, we demonstrate the microwave‐assisted synthesis of three molecular weight varieties of poly(ethylene glycol) dimethacrylate (PEGDMA) with different mechanical and thermal properties and the rapid photo of them using 1‐hydroxy‐cyclohexyl‐phenyl‐ketone (Irgacure 184) as UV photoinitiator. The effects of the poly(ethylene glycol) molecular weight and degree of acrylation on swelling, mechanical, and rheological properties of hydrogels were investigated. The biodegradability of the PEGDMA hydrogels, as well as the ability to grow and proliferate cells, was examined for its viability as a scaffold in tissue engineering. Altogether, the biomaterial hydrogel properties open the way for applications in the field of regenerative medicine for functional scaffolds and tissues. [ABSTRACT FROM AUTHOR]

Gelatin and chitosan polysaccharides were chemically modified to get methacrylate functionality to obtain biocompatible hydrogels for use as tissue engineering scaffolds. The methacrylation reaction was verified by 1H‐NMR. The degree of methacrylation was varied from 7% to 40% by changing the molar ratio of polysaccharide to methacrylic anhydride and the type of polysaccharide utilized. After the modification, polysaccharide‐based hydrogels were prepared by free‐radical polymerization in the presence of UV light and Irgacure 184 as a photoinitiator. The physical, chemical, and mechanical performances of the hydrogels were further characterized. Also, the biodegradability and the viability of the polysaccharide hydrogels were investigated using fibroblast cells. These cells were seeded directly onto the hydrogel surface, populated the entirety of the hydrogel, and remained viable for up to 1 week. Altogether, the modified polysaccharides exhibit the properties which make them crucial for applications in the field of regenerative medicine. [ABSTRACT FROM AUTHOR]