The presence of podoplanin expression in cancer-associated fibroblasts correlates with aggressive behavior in melanoma and might therefore serve as a useful prognostic factor for patients with melanoma.

BackgroundSarcoidosis is a chronic and systemic inflammatory disease, in which patients present with noncaseating epithelioid granulomas. Cutaneous lesions of sarcoidosis develop in 9% to 35% of all sarcoidosis patients and comprise various clinical subtypes. It usually affects multiple organs and has a variable clinical course; this is called systemic sarcoidosis (SS). However, occasionally, it only affects the skin and is then called cutaneous sarcoidosis (CS). Recent observations suggest that serum levels of soluble CD163 correlate with immune cell activity in sarcoidosis patients; however, the contribution of M1 and M2 macrophages toward disease progression remains unclear.MethodsWe evaluated macrophage phenotypes histopathologically using skin biopsy samples obtained from patients with CS (n = 8) and SS (n = 31) and performed immunostaining with CD68, iNOS (M1 macrophages), PD‐L1, and CD163 (M2 macrophages).ResultsThe density of CD163‐positive cells in the SS group was significantly higher than that in the CS group. There was no significant correlation between the CD163 (+) cell density and serum angiotensin‐converting enzyme level, serum calcium, or tuberculin reaction.ConclusionsImmunostaining for CD163 may be a novel and useful marker to predict systemic involvement in patients with cutaneous lesions of epithelioid granulomas.

A B S T R A C TBackground: Nanoparticle-loaded delivery systems have attracted much attention recently. Poly(lacticco-glycolic acid) (PLGA) is one of the most successful biodegradable polymers for biomedical applications. There are only a few studies on the treatment of dermal fibrosis with sustained-release drugs. Peroxisome proliferator-activated receptor-g (PPAR-g) plays an important role in endogenous anti-fibrotic defense mechanisms. Recent studies have suggested that pioglitazone, a synthetic PPAR-g activator, has effects beyond reducing blood sugar and it can reduce fibrosis and inflammation when used systemically. Objective: We aimed to assess the effects of local injections of pioglitazone-loaded PLGA nanoparticles (PGN-NP) on an experimental sclerosis and to demonstrate the in vivo pharmacokinetics of subcutaneously administered PLGA nanoparticles. Methods: Locally injectable PGN-NP were prepared and subcutaneously administered to bleomycin (BLM)-induced scleroderma model mice. The effect of pioglitazone was also evaluated with cultured fibroblasts. Coumarin-6-loaded fluorescent PLGA nanoparticles (FL-NP) and silicon naphthalocyanineloaded near-infrared PLGA nanoparticles (NIR-NP) were used to demonstrate in vitro cellular uptake by cultured fibroblasts and the in vivo pharmacokinetics of subcutaneously administered nanoparticles. Results: Weekly subcutaneous injections of PGN-NP attenuated skin fibrosis in BLM-induced scleroderma model mice. Pioglitazone significantly suppressed migration ability and TGF-β-mediated myofibroblast differentiation in cultured fibroblasts. FL-NP were internalized into cultured fibroblasts within 60 min, and PGN-NP-primed fibroblasts expressed anti-fibrotic phenotypes. Subcutaneously injected NIR-NP remained in the vicinity of the injection site more than non-particulate silicon naphthalocyanine. Conclusion: These results provide a basis for the development of new treatments for dermal fibrosis and a better understanding of the potential of PLGA nanoparticles in dermatology.

The presence of podoplanin expression in peritumoral keratinocytes correlates with aggressive behavior in EMPD and might therefore serve as a useful prognostic marker for patients with EMPD.

No abstract