JNJ-10229570-AAA

In this study, the plate casting method was successfully used to prepare biocomposite films containing EPS from probiotic Enterococcus faecium MC-5 in combination with PVA and chitosan. The findings demonstrated that EPS was uniformly distributed in the film matrices and significantly improved the physicochemical properties of the resulting composite films. The development of intermolecular connections between the polymers was detected by high tensile strength and low water vapour transmission rate. EPS plays an important role in limiting the passage of UV- and visible light radiations through the films. FT-IR analysis was used to determine the molecular compatibility between the functional groups of the blended films made up of chitosan-EPS and PVA-EPS. The TGA results showed that composite films have a significant degree of thermal stability. The presence of amorphous peaks in the composite film was confirmed by XRD analysis. The EPS blended films displayed a greater antioxidant property than the PVA and chitosan films, as determined by DPPH and hydroxyl radical scavenging activities. Interestingly, the EPS-derived films showed enhanced metal chelation activity and strong antibacterial properties against Listeria monocytogenes and Staphylococcus aureus. EPS-based composite films performed better than chitosan and PVA films in terms of degradation rate. The overall functional characteristics of the EPS blended films suggested that they could be used as a packaging material to replace or reduce the use of conventional petroleum-based packaging materials.

The melanocortin receptor-5 (MC5R) is present in human sebaceous glands, where it is expressed in differentiated sebocytes only. The targeted disruption of MC5R in mice resulted in reduced sebaceous lipid production and a severe defect in water repulsion.

To investigate the physiological function of MC5R in human sebaceous glands.

A novel MC1R and MC5R antagonist (JNJ-10229570) was used to treat primary human sebaceous cells or human skins grafted onto severe combined immunodeficient (SCID) mice. Transcription profiling, lipid analyses, and histological and immunohistochemical staining were used to analyze the effect of MC5R inhibition on sebaceous gland differentiation and sebum production.

JNJ-10229570 dose dependently inhibited the production of sebaceous lipids in cultured primary human sebocytes. Topical treatment with JNJ-10229570 of human skins transplanted onto SCID mice resulted in a marked decrease in sebum-specific lipid production, sebaceous gland's size and the expression of the sebaceous differentiation marker epithelial-membrane antigen (EMA). Treatment with flutamide, a known inhibitor of sebum production, gave similar results, validating the human skin/SCID mouse experimental system for sebaceous secretion studies.

Our data suggest that antagonists of MC1R and MC5R could be effective sebum suppressive agents and might have a potential for the treatment of acne and other sebaceous gland pathologies.