MicroRNA-29 is an anti-fibrotic miRNA whose expression is downregulated in multiple fibrotic indications including in cutaneous scars and keloids. Its target genes include numerous collagens and other extracellular matrix molecules, suggesting that restoration of miR-29 expression in a skin wound or at the site of an excised scar could have a therapeutic benefit by reducing scarring and/or preventing scar regrowth. An oligonucleotide mimic of miR-29b (MRG-201) was studied in vivo in mouse, rats and rabbits as well as in vitro in human skin fibroblasts to identify a set of conserved pharmacodynamic biomarkers in the skin. MRG-201 was then evaluated in a Phase 1 double-blinded within-patient randomized clinical trial in 53 normal healthy volunteers (NCT02603224). Expression of miR-29b and its pharmacodynamic biomarkers was assessed in untreated skin incisions and following single or multiple administrations of MRG-201 at the site of a sutured skin incision. miR-29b expression was significantly decreased and direct miR-29 target genes were significantly upregulated with incision alone. Intradermal administration of MRG-201 resulted in a high local concentration of miR-29b with low systemic exposure and good safety/tolerability at all doses tested. Pharmacodynamic activity was seen after MRG-201 treatment: single and multiple doses of MRG-201 reduced collagen mRNA expression as compared to a placebo injected incision in the same subject. Additionally, multiple administrations of MRG-201 reduced fibroplasia as assessed by histopathology (p < 0.01). These findings support further investigation of MRG-201 as a novel therapeutic to inhibit scar formation or prevent hypertrophic scar or keloid recurrence following excision.
Traffic-related air pollution is associated with clinical signs of extrinsic skin aging in Caucasian and Han Chinese. In this regard, two mechanistic pathways have been suggested: (i) air pollutants may either act directly on human skin or (ii), after inhalation, may cause lung inflammation, which may spill over into the blood circulation and thereby indirectly affect skin. We tested the latter hypothesis by conducting a mediation analysis. We assessed clinical signs of extrinsic skin aging by a validated score (SCINEXA TM ), markers for lung inflammation in induced sputum (IS) and in exhaled breath condensate (EBC), as well as serum levels of inflammatory cytokines. These parameters were determined in 402 Caucasians from the German SALIA cohort and 1,406 Han Chinese from the Taizhou study cohort (no IS or EBC analysis). Air pollution data were measured in Germany as part of the ESCAPE campaign in 2009 or obtained in China from monitoring stations of the Chinese EPA. Inflammation markers in IS and EBC were positively associated with pigment spots on cheeks (NO derivatives in IS: p¼0.0485, and in EBC: p < 0.0001). The mediation analysis, however, revealed that lung inflammation markers explained less than 10% of the association between air pollution exposure and pigment spots on cheeks. No association was detectable between inflammatory markers in serum, air pollution, and pigment spot formation. We therefore conclude that air pollution-induced pigment spot formation is not mediated by lung inflammation, but might rather be the result of direct effects of air pollutants on skin. IL Hepatitis (B and C) is an important determinant, especially with biologic agents for psoriasis, presumably related to the potential for reactivation of Hepatitis B. However, reports on prevalence are inconsistent. The aim of this study was to determine the prevalence of hepatitis (B and C) in psoriasis patients in a large single center, U.S patient population by searching an EMR data repository. The study cohort consisted of all adults aged 18-89 years who underwent hepatitis B or C serology screening (September 2010 through September 2016). Psoriasis and hepatitis diagnoses were identified by ICD Codes (ICD9 and ICD10 codes: 696.1, L40.0-L40.4, L40.8, L40.9 and base code B18, B19, 070, respectively). The control cohort consisted of all patients within the same database with no psoriasis diagnosis. Statistical analysis was performed using logistic regression, from which crude and adjusted (for age, gender, and race) analyses were calculated. A total of 114,860 patients (57.6% female, 49.7% Caucasian) underwent hepatitis (B and/or C) screening. Of 2,591 patients with psoriasis, 48 (1.8%) had positivity for hepatitis (B and/or C) compared to 2,775 (2.5%) patients in the non-psoriasis cohort (n¼112,269). Prevalence of hepatitis (B and C) was significantly lower in psoriasis compared to non-psoriasis cohort, both in the crude and adjusted analyses (crude OR¼0.745, 95% CI ¼ 0.558-0.993, p¼0.045; adjusted OR¼0.664, 95% CI ¼ 0.497-0.888, p¼0.0...
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