Pigmentation control in pregnancy-induced melasma: Clinical assessment of a non-hydroquinone, non-retinol pigment-correcting serum.

BACKGROUND: Melasma is an acquired disorder that results in irregular brown patches on the skin that can occur due to hormonal changes. Although pregnancy-induced melasma is usually temporary, it can become a chronic condition, with significant negative impact on quality of life (QoL). AIMS: Determine the efficacy and tolerability of a topical, non-hydroquinone, non-retinol pigment-correcting serum (LYT2) for the treatment of pregnancy-induced melasma. METHODS: This 12-week, single-center clinical trial enrolled 34 non-pregnant women who developed mild to severe facial melasma following a previous pregnancy (mean age, 42 years). LYT2 was applied twice daily to facial skin for 12 weeks in addition to a basic skincare regimen. Outcomes included changes from baseline in skin physiology parameters, such as brightness (L*), using objective digital image analysis, investigator-rated Overall Hyperpigmentation scale, Global Improvement, and Melasma Area and Severity Index (MASI), as well as subject-assessed Melasma Quality of Life Scale. Subjects also completed a questionnaire on self-perceived efficacy and attributes of the study product. Tolerability was assessed by the investigators (erythema, scaling, and edema) and subjects (burning/stinging and itching). Clinical assessments were conducted at baseline and Weeks 4, 8, and 12. RESULTS: LYT2 provided statistically significant reductions in overall hyperpigmentation scores as early as Week 4 (-5.8% change from baseline) and continued through Week 12 (-14.6% change from baseline; all p < 0.001). Significant improvements in MASI scores and QoL were also achieved following LYT2 treatment, which was well tolerated. CONCLUSIONS: LYT2 represents a new efficacious alternative to hydroquinone-based treatments for pregnancy-induced melasma.

Efficacy and Tolerability of a Novel Topical Treatment for Neck: A Randomized, Double-blind, Regimen-Controlled Study.

The neck plays a telling role as an age indicator. Due to its anatomy and function, neck skin ages differently than facial skin and special considerations need to be taken when providing treatment. A randomized, double-blind, regimen-controlled study was conducted to assess the efficacy and tolerability of a novel topical cosmetic cream (NCC) specifically tailored to address the signs of skin aging of the neck and décolletage. Twice daily application of NCC significantly improved skin sagging/laxity of the neck as well as the appearance of fine and coarse lines/wrinkles, crepiness, tactile roughness, overall skin texture, hyperpigmentation, skin tone evenness, and radiance. NCC also significantly improved the appearance of fine and coarse lines/wrinkles, tactile roughness, hyperpigmentation, skin tone evenness, and radiance of the décolletage. Investigator assessments were corroborated by objective cutometer measurements that demonstrated improved skin firmness and elasticity. In vitro analysis in human 3D skin models show that stimulation of neocollagenesis and neoelastogenesis as well as support of cellular proteostasis through proteasome and autophagy activation are potential mechanisms of action for the observed clinical outcomes. J Drugs Dermatol. 2021;20(2):184-191. doi:10.36849/JDD.5819 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Coronin Enhances Actin Filament Severing by Recruiting Cofilin to Filament Sides and Altering F-Actin Conformation.

High rates of actin filament turnover are essential for many biological processes and require the activities of multiple actin-binding proteins working in concert. The mechanistic role of the actin filament severing protein cofilin is now firmly established; however, the contributions of other conserved disassembly-promoting factors including coronin have remained more obscure. Here, we have investigated the mechanism by which yeast coronin (Crn1) enhances F-actin turnover. Using multi-color total internal reflection fluorescence microscopy, we show that Crn1 enhances Cof1-mediated severing by accelerating Cof1 binding to actin filament sides. Further, using biochemical assays to interrogate F-actin conformation, we show that Crn1 alters longitudinal and lateral actin-actin contacts and restricts opening of the nucleotide-binding cleft in actin subunits. Moreover, Crn1 and Cof1 show opposite structural effects on F-actin yet synergize in promoting release of phalloidin from filaments, suggesting that Crn1/Cof1 co-decoration may increase local discontinuities in filament topology to enhance severing.

Drebrin-induced stabilization of actin filaments.

Drebrin is a mammalian neuronal protein that binds to and organizes filamentous actin (F-actin) in dendritic spines, the receptive regions of most excitatory synapses that play a crucial role in higher brain functions. Here, the structural effects of drebrin on F-actin were examined in solution. Depolymerization and differential scanning calorimetry assays show that F-actin is stabilized by the binding of drebrin. Drebrin inhibits depolymerization mainly at the barbed end of F-actin. Full-length drebrin and its C-terminal truncated constructs were used to clarify the domain requirements for these effects. The actin binding domain of drebrin decreases the intrastrand disulfide cross-linking of Cys-41 (in the DNase I binding loop) to Cys-374 (C-terminal) but increases the interstrand disulfide cross-linking of Cys-265 (hydrophobic loop) to Cys-374 in the yeast mutants Q41C and S265C, respectively. We also demonstrate, using solution biochemistry methods and EM, the rescue of filament formation by drebrin in different cases of longitudinal interprotomer contact perturbation: the T203C/C374S yeast actin mutant and grimelysin-cleaved skeletal actin (between Gly-42 and Val-43). Additionally, we show that drebrin rescues the polymerization of V266G/L267G, a hydrophobic loop yeast actin mutant with an impaired lateral interface formation between the two filament strands. Overall, our data suggest that drebrin stabilizes actin filaments through its effect on their interstrand and intrastrand contacts.

Mapping of drebrin binding site on F-actin.

Drebrin is a filament-binding protein involved in organizing the dendritic pool of actin. Previous in vivo studies identified the actin-binding domain of drebrin (DrABD), which causes the same rearrangements in the cytoskeleton as the full-length protein. Site-directed mutagenesis, electron microscopic reconstruction, and chemical cross-linking combined with mass spectrometry analysis were employed here to map the DrABD binding interface on actin filaments. DrABD could be simultaneously attached to two adjacent actin protomers using the combination of 2-iminothiolane (Traut's reagent) and MTS1 [1,1-methanediyl bis(methanethiosulfonate)]. Site-directed mutagenesis combined with chemical cross-linking revealed that residue 238 of DrABD is located within 5.4 A from C374 of actin protomer 1 and that native cysteine 308 of drebrin is near C374 of actin protomer 2. Mass spectrometry analysis revealed that a zero-length cross-linker, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, can link the N-terminal G-S extension of the recombinant DrABD to E99 and/or E100 on actin. Efficient cross-linking of drebrin residues 238, 248, 252, 270, and 271 to actin residue 51 was achieved with reagents of different lengths (5.4-19 A). These results suggest that the "core" DrABD is centered on actin subdomain 2 and may adopt a folded conformation upon binding to F-actin. The results of electron microscopic reconstruction, which are in a good agreement with the cross-linking data, revealed polymorphism in DrABD binding to F-actin and suggested the existence of two binding sites. These results provide new structural insight into the previously observed competition between drebrin and several other F-actin-binding proteins.