A Microbiome-Based Index for Assessing Skin Health and Treatment Effects for Atopic Dermatitis in Children.

A quantitative and objective indicator for skin health via the microbiome is of great interest for personalized skin care, but differences among skin sites and across human populations can make this goal challenging. A three-city (two Chinese and one American) comparison of skin microbiota from atopic dermatitis (AD) and healthy pediatric cohorts revealed that, although city has the greatest effect size (the skin microbiome can predict the originated city with near 100% accuracy), a microbial index of skin health (MiSH) based on 25 bacterial genera can diagnose AD with 83 to ∼95% accuracy within each city and 86.4% accuracy across cities (area under the concentration-time curve [AUC], 0.90). Moreover, nonlesional skin sites across the bodies of AD-active children (which include shank, arm, popliteal fossa, elbow, antecubital fossa, knee, neck, and axilla) harbor a distinct but lesional state-like microbiome that features relative enrichment of Staphylococcus aureus over healthy individuals, confirming the extension of microbiome dysbiosis across body surface in AD patients. Intriguingly, pretreatment MiSH classifies children with identical AD clinical symptoms into two host types with distinct microbial diversity and treatment effects of corticosteroid therapy. These findings suggest that MiSH has the potential to diagnose AD, assess risk-prone state of skin, and predict treatment response in children across human populations.IMPORTANCE MiSH, which is based on the skin microbiome, can quantitatively assess pediatric skin health across cohorts from distinct countries over large geographic distances. Moreover, the index can identify a risk-prone skin state and compare treatment effect in children, suggesting applications in diagnosis and patient stratification

A microbiome-based index for assessing skin health and treatment effects for atopic dermatitis in children

A quantitative and objective indicator for skin health via the microbiome is of great interest for personalized skin care, but differences among skin sites and across human populations can make this goal challenging. A three-city (two Chinese and one American) comparison of skin microbiota from atopic dermatitis (AD) and healthy pediatric cohorts revealed that, although city has the greatest effect size (the skin microbiome can predict the originated city with near 100% accuracy), a microbial index of skin health (MiSH) based on 25 bacterial genera can diagnose AD with 83 to similar to 95% accuracy within each city and 86.4% accuracy across cities (area under the concentration-time curve [AUC], 0.90). Moreover, nonlesional skin sites across the bodies of AD-active children (which include shank, arm, popliteal fossa, elbow, antecubital fossa, knee, neck, and axilla) harbor a distinct but lesional state-like microbiome that features relative enrichment of Staphylococcus aureus over healthy individuals, confirming the extension of microbiome dysbiosis across body surface in AD patients. Intriguingly, pretreatment MiSH classifies children with identical AD clinical symptoms into two host types with distinct microbial diversity and treatment effects of corticosteroid therapy. These findings suggest that MiSH has the potential to diagnose AD, assess risk-prone state of skin, and predict treatment response in children across human populations. IMPORTANCE MiSH, which is based on the skin microbiome, can quantitatively assess pediatric skin health across cohorts from distinct countries over large geographic distances. Moreover, the index can identify a risk-prone skin state and compare treatment effect in children, suggesting applications in diagnosis and patient stratification

Topical tranexamic acid improves the permeability barrier in rosacea

Objective: To evaluate the influence of tranexamic acid on epidermal permeability barrier function in rosacea and its potential mechanisms. Methods: A randomized, vehicle controlled, split-face study was performed on 30 rosacea patients. This study involved 2 weeks of 3% tranexamic acid solution treatment and vehicle control treatment. Skin physiological parameters, including skin surface pH, stratum corneum hydration, and transepidermal water loss, were measured. The expression of protease-activated receptor 2 (PAR-2) in rosacea and normal skin samples was assessed with immunohistochemical staining. The expression of PAR-2 in HaCaT keratinocytes was determined using reverse transcription polymerase chain reaction after stimulation with tranexamic acid. Changes of intracellular calcium induced by PAR-2 activation were measured using Fluo-4 NW calcium assay. Results: Individuals with rosacea expressed a higher baseline level of PAR-2 compared with normal skin. Tranexamic acid improved the permeability barrier function in rosacea patients and inhibited calcium mobilization in keratinocytes induced by PAR-2 activation. The PAR-2 expression was not altered by tranexamic acid stimulation. Conclusion: Topical tranexamic acid could improve the epidermal permeability barrier function and clinical signs of rosacea, likely resulting from inhibition of PAR-2 activation and consequent calcium influx. Thus, tranexamic acid could serve as an adjuvant therapy for rosacea

Pharmacophore modeling and virtual screening for the discovery of new type 4 cAMP phosphodiesterase (PDE4) inhibitors.

Type 4 cAMP phosphodiesterase (PDE4) inhibitors show a broad spectrum of anti-inflammatory effects in almost all kinds of inflamed cells, by an increase in cAMP levels which is a pivotal second messenger responsible for various biological processes. These inhibitors are now considered as the potential drugs for treatment of chronic inflammatory diseases. However, some recently marketed inhibitors e.g., roflumilast, have shown adverse effects such as nausea and emesis, thus restricting its use. In order to identify novel PDE4 inhibitors with improved therapeutic indexes, a highly correlating (r = 0.963930) pharmacophore model (Hypo1) was established on the basis of known PDE4 inhibitors. Validated Hypo1 was used in database screening to identify chemical with required pharmacophoric features. These compounds are further screened by using the rule of five, ADMET and molecular docking. Finally, twelve hits which showed good results with respect to following properties such as estimated activity, calculated drug-like properties and scores were proposed as potential leads to inhibit the PDE4 activity. Therefore, this study will not only assist in the development of new potent hits for PDE4 inhibitors, but also give a better understanding of their interaction with PDE4. On a wider scope, this will be helpful for the rational design of novel potent enzyme inhibitors

The correlation graph between experimental and estimated activity values based on Hypo1.

<p>The correlation graph between experimental and estimated activity values based on Hypo1.</p

Alignment of twelve hit compounds with the best pharmacophore model, Hypo1.

<p>Pharmacophore features are color-coded: cyan, hydrophobic (HY); orange, ring aromatic (RA); green, hydrogen bond acceptor (HBA).</p

Chemical structures of PDE4 inhibitors in the training set.

<p>Chemical structures of PDE4 inhibitors in the training set.</p

The best HypoGen pharmacophore model, Hypo1.

<p>(A) Chemical features present in Hypo 1. (B) 3D spatial relationship and geometric parameters of Hypo1. Pharmacophore features are color-coded (cyan, hydrophobic; orange, ring aromatic; green, hydrogen bond acceptor). Pharmacophore features are color-coded: cyan, hydrophobic (HY); orange, ring aromatic (RA); green, hydrogen bond acceptor (HBA).</p