Central for wound healing is the formation of granulation tissue, which largely consists of collagen and whose importance stretches past wound healing, including being implicated in both fibrosis and skin aging. Cyclophilin D (CyD) is a mitochondrial protein that regulates the permeability transition pore, known for its role in apoptosis and ischemia-reperfusion. To date, the role of CyD in human wound healing and collagen generation has been largely unexplored. Here, we show that CyD was upregulated in normal wounds and venous ulcers, likely adaptive as CyD inhibition impaired reepithelialization, granulation tissue formation, and wound closure in both human and pig models. Overexpression of CyD increased keratinocyte migration and fibroblast proliferation, while its inhibition reduced migration. Independent of wound healing, CyD inhibition in fibroblasts reduced collagen secretion and caused endoplasmic reticulum collagen accumulation, while its overexpression increased collagen secretion. This was confirmed in a Ppif -KO mouse model, which showed a reduction in skin collagen. Overall, this study revealed previously unreported roles of CyD in skin, with implications for wound healing and beyond.

Despite suppressive anti-retroviral therapy (ART), some older people with HIV show adverse ageing phenotypes, and the underlying mechanisms remain incompletely understood. We recruited 30 men with HIV aged ≥ 50 years and 15 well-matched men without HIV and performed histological analyses on skeletal muscle biopsies and plasma biomarker measurement, in combination with clinical and functional assessments. Men with HIV showed higher frequencies of frailty, pre-frailty, sarcopenia, and pre-sarcopenia when compared to men without HIV. When assessing skeletal muscle, men with HIV had decreased mitochondrial complex I and IV protein abundance and myofibre regeneration, whilst fibrosis was increased, and plasma TNFα and MCP-4 levels were elevated. Spearman correlation analyses suggested that inflammation and mitochondrial respiratory chain deficiency may result in a damage response in skeletal muscle with resolution by fibrosis rather than regeneration. These findings thus provide plausible rationales for adverse ageing phenotypes in older men with HIV, including frailty and sarcopenia.

The purpose of this study is to screen for and test the effectiveness of dantrolene (Dl) as a novel drug to improve Darier disease (DD). By using | POSTER