Background: Cathepsin G, a serine protease that is activated by ultraviolet (UV) radiation, increases matrix metalloproteinase-1 (MMP-1) expression in fibroblasts through fibronectin (Fn) fragmentation and promotes the conversion of proMMP-1 to active MMP-1. Objectives: This study investigated whether [2-[3-[[(1-benzoyl-4-piperidinyl)methylamino]carbonyl]-2-naphthalenyl]-1-(1-naphthalenyl)-2-oxoethyl]-phosphonic acid (KPA), a cathepsin G inhibitor, plays any role in extracellular matrix (ECM) damage in an in vitro 3D dermal equivalent (DE) and an in vivo ultraviolet B (UVB)-irradiated hairless mice. Methods: We examined the potential ECM-protective effects of a cathepsin G inhibitor in an in vitro 3D DE model and an in vivo UVB-irradiated hairless mouse skin model. Results: Among five known serine protease inhibitors, KPA showed the strongest potency and selectivity against cathepsin G. KPA inhibited the cathepsin G-mediated MMP-1 increase and alleviated the downregulation of mRNAs encoding collagen and tissue inhibitor of matrix metalloproteinase-1 in an in vitro 3D DE model. Most importantly, topical application of KPA (0.025%) to the dorsal skin of hairless mice enhanced collagen expression and attenuated UVB-induced Fn fragmentation and upregulation of MMP-2 and MMP-9 activities. Conclusions: Cathepsin G inhibitors may be useful for the prevention of UVB-induced photoaging through amelioration of ECM damage and MMP upregulation.

We report the first case of subcutaneous hyalohyphomycosis caused by the genus Cephalotheca, which has not been reported to cause human infection. A 67-year-old immunocompetent farmer presented with a 10-year history of verrucous erythematous plaques on the right foot dorsum, great toe, heel and sole. Histopathology of the lesions revealed chronic granulomatous inflammation with numerous nonpigmented fungal spores in the dermis. Cultures of biopsy specimens on Sabouraud's dextrose agar for 2 weeks developed into yellowish brown, velvety colonies that subsequently turned black after 8 weeks because of the production of black cleistothecia indicating the teleomorph. On the basis of mycological features, scanning electron microscopic morphology and molecular analysis data, a new species of Cephalotheca was identified and designated Cephalotheca foveolata. Because there was no response to the antifungal agents administered, the patient was successfully treated by surgical excision with skin graft.

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