Nitric Oxide-Releasing Nanoparticles Prevent Propionibacterium acnes-Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response.

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we used an established nanotechnology capable of generating/releasing NO over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, although human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, tumor necrosis factor-α (TNF-α), IL-8, and IL-6 from human monocytes, and IL-8 and IL-6 from human keratinocytes, respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α nor IL-6 secretion, nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1β secretion was through inhibition of caspase-1 and IL-1β gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response

Epidemiology and treatment of angiolymphoid hyperplasia with eosinophilia (ALHE): A systematic review

Current knowledge of angiolymphoid hyperplasia with eosinophilia (ALHE) derives from retrospective reports and case series, leading to a nonevidence-based treatment approach. We sought to systematically review the literature relating to cutaneous ALHE to estimate its epidemiology and treatment outcomes. A literature search of PubMed, EMBASE, Web of Science, and Google Scholar was conducted. Articles detailing cases of histologically confirmed cutaneous ALHE were included. In all, 416 studies were included in the review, representing 908 patients. There was no sex predominance among patients with ALHE. Mean age at presentation was 37.6 years. There was a significant association between presence of multiple lesions and pruritus, along with bleeding. Surgical excision was the most commonly reported treatment for ALHE. Treatment failure was lowest for excision and pulsed dye laser. Mean disease-free survival after excision was 4.2 years. There were higher rates of recurrence postexcision with earlier age of onset, longer duration of disease, multiple lesions, bilateral lesions, pruritus, pain, and bleeding. Potential for publication bias is a limitation. Surgical excision appears to be the most effective treatment for ALHE, albeit suboptimal. Pulsed dye and other lasers may be effective treatment options. More studies are needed to improve the treatment of ALHE

Trichophyton rubrum is inhibited by free and nanoparticle encapsulated curcumin by induction of nitrosative stress after photodynamic activation.

Antimicrobial photodynamic inhibition (aPI) utilizes radical stress generated from the excitation of a photosensitizer (PS) with light to destroy pathogens. Its use against Trichophyton rubrum, a dermatophytic fungus with increasing incidence and resistance, has not been well characterized. Our aim was to evaluate the mechanism of action of aPI against T. rubrum using curcumin as the PS in both free and nanoparticle (curc-np) form. Nanocarriers stabilize curcumin and allow for enhanced solubility and PS delivery. Curcumin aPI, at optimal conditions of 10 μg/mL of PS with 10 J/cm² of blue light (417 ± 5 nm), completely inhibited fungal growth (p<0.0001) via induction of reactive oxygen (ROS) and nitrogen species (RNS), which was associated with fungal death by apoptosis. Interestingly, only scavengers of RNS impeded aPI efficacy, suggesting that curcumin acts potently via a nitrosative pathway. The curc-np induced greater NO˙ expression and enhanced apoptosis of fungal cells, highlighting curc-np aPI as a potential treatment for T. rubrum skin infections

Evaluation of ROS and RNS production after aPI.

<p>Detection of ROS levels following aPI, expressed as a <b>(a)</b> representative histogram and <b>(d)</b> cumulative bar plot. Detection of NO^• levels following aPI, expressed as a <b>(b)</b> representative histogram and <b>(e)</b> cumulative bar plot. Detection of ONOO⁻ levels following aPI, expressed as a <b>(c)</b> representative histogram and <b>(f)</b> cumulative bar plot. Dark toxicity controls did not differ significantly from untreated <i>T</i>. <i>rubrum</i> (data not represented). ***Compared to untreated control. ^###Compared to curc group. <b>MFI</b>. Mean fluorescence intensity. ***,^###p < 0.0001. Each treatment per group was performed in triplicate and are a composite of two independent experiments. The results are expressed as the mean ± SEM.</p

Groups and conditions for performing antimicrobial photodynamic therapy.

<p>Groups and conditions for performing antimicrobial photodynamic therapy.</p

Evaluation of aPI mechanism of action.

<p><b>(a)</b> Treatment with ONOO⁻ scavenger (FeTPPs). <b>(b)</b> Treatment with NO^• scavenger (Carboxy-PTIO). <b>(c)</b> Apoptosis assay performed after aPI. ***Compared to aPI treatment in the absence of incubation with scavengers. *Compared to untreated <i>T</i>. <i>rubrum</i> control. *p< 0.05, ***p< 0.0001. Each treatment per group was performed in triplicate and data are a composite of two independent experiments. The results are expressed as mean ± SEM.</p

Phagocytosis assay.

<p>CFU quantification of macrophages challenged with <i>T</i>. <i>rubrum</i> cells and treated with aPI therapy. ^# Compared to untreated control (C), dark toxicity and blue light 10 J/cm² (B.L.) controls. * Compared to all other groups. B.L. Blue light 10 J/cm² (17 minutes). *,^# p < 0.05. Each treatment per group was performed in triplicate and data is a composite of two independent experiments. The results are expressed as the mean ± SEM.</p