The Arabidopsis chromatin regulator MOM1 is a negative component of the defense priming induced by AZA, BABA and PIP.

In plants, the establishment of broad and long-lasting immunity is based on programs that control systemic resistance and immunological memory or "priming". Despite not showing activated defenses, a primed plant induces a more efficient response to recurrent infections. Priming might involve chromatin modifications that allow a faster/stronger activation of defense genes. The Arabidopsis chromatin regulator "Morpheus Molecule 1" (MOM1) has been recently suggested as a priming factor affecting the expression of immune receptor genes. Here, we show that mom1 mutants exacerbate the root growth inhibition response triggered by the key defense priming inducers azelaic acid (AZA), ß-aminobutyric acid (BABA) and pipecolic acid (PIP). Conversely, mom1 mutants complemented with a minimal version of MOM1 (miniMOM1 plants) are insensitive. Moreover, miniMOM1 is unable to induce systemic resistance against Pseudomonas sp. in response to these inducers. Importantly, AZA, BABA and PIP treatments reduce the MOM1 expression, but not miniMOM1 transcript levels, in systemic tissues. Consistently, several MOM1-regulated immune receptor genes are upregulated during the activation of systemic resistance in WT plants, while this effect is not observed in miniMOM1. Taken together, our results position MOM1 as a chromatin factor that negatively regulates the defense priming induced by AZA, BABA and PIP.

Azelaic acid-loaded nanoemulsion with hyaluronic acid - a new strategy to treat hyperpigmentary skin disorders.

OBJECTIVE: To develop an azelaic acid (AzA)-loaded nanoemulsion with hyaluronic acid (HA) as a double targeting strategy to increase drug retention and tyrosinase inhibition activity. SIGNIFICANCE: Dermic melasma is a recalcitrant disease. Therefore, the development of new technologies that allow a deeper penetration in the skin while enhancing the efficacy of a safe and well-known dermatological active, like AzA, is a very promising alternative to improve the treatment of this disease. METHODS: An oil-in-water nanoemulsion was developed and characterized according to its droplet size distribution, zeta potential, pH value, drug content, encapsulation efficiency, spectroscopic characteristics, morphology, and stability. In vitro mushroom tyrosinase inhibition assay, cytotoxicity, and permeation studies were performed. A descriptive sensory evaluation was also carried out. RESULTS: Drug content was 10 mg/ml, particle size 419 ± 23 nm with monomodal distribution, encapsulation efficiency was 84.65%, zeta potential -10.9 ± 0.44 mV and pH 5.01 ± 0.01. The nanoemulsion was stable for 30 days (30 °C/65% RH). The nanoemulsion decreased tyrosinase activity and permeated through the skin, reaching viable epidermis and dermis and did not show signs of cytotoxicity. Sensory evaluation profile showed a higher spreadability with lesser whitening residue. CONCLUSION: The nanoemulsion presented characteristics within the nanoscale and reached the deeper layers of the skin while improving in vitro tyrosinase inhibition; hence, it could be a promising treatment to dermic melasma.

Modulation of Toll Like Receptor-2 on sebaceous gland by the treatment of adult female acne.

Adult female acne is a chronic inflammatory, immune-mediated disease that affects the pilosebaceous unit in women in their 20s to 40s, and is considered different from acne vulgaris. Propionibacterium acnes is recognized by TLR-2, resulting in activation of this receptor and an inflammatory response through the NFκ B pathway. This therapeutic, interventional, open, randomized, evaluator-blinded and comparative trial included 38 adult women with moderate facial acne and 10 age-matched controls, all aged between 26 and 44 years. Two treatments were performed over six months: 15% azelaic acid gel (AA) bid (n = 18) and oral contraceptive (COC) drospirenone 3 mg/ethinylestradiol .02 mg (n = 20). Biopsies were taken at baseline (control, lesion, perilesional) and at the conclusion (lesion and perilesional) of the study to evaluate TLR-2 expression by immunohistochemistry. Lesion count and blind photographic evaluation were used for efficacy. The groups were homogeneous: 70% of lesions were located in the submandibular area, 95% of participants had inflammatory lesions; of these, 50% had persistent and 50% had late-onset acne. The mean ages were 33.7 ± 5.5 and 33.1 ± 5.3 years (COC and AA group, respectively). A moderate clinical improvement was observed in both groups. No difference in TLR-2 expression in the lesion or perilesional areas was observed; however, reduced TLR-2 expression was seen in the control group. A significant reduction in expression was observed after both treatments, with no difference between the groups. This finding suggests an anti-inflammatory effect of COCs and AA in adult female acne, via modulation of the TLR-2 receptor.

A randomized comparative trial of a combined oral contraceptive and azelaic acid to assess their effect on sleep quality in adult female acne patients.

Several studies have reported an increase in the prevalence of adult female acne. This subtype of acne presents particular characteristics, and can be triggered by several factors such as smoking, stress, the use of oily cosmetics and even by poor sleep. Sleep quality is related to well-being and the maintenance of body homeostasis. In addition, several skin diseases present a bidirectional relationship with sleep, demonstrating an important connection between skin and the central nervous system. With this in mind, we aimed to compare the effect of two types of treatment for adult female acne (azelaic acid or a combined oral contraceptive) on sleep quality and on concentrations of stress hormones. Also, we proposed to assess the correlation of sleep and hormonal parameters with acne severity. In order to do this, 32 women underwent a clinical evaluation, completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire and had their blood collected for hormone assays. These procedures were performed at baseline and after 6 months of treatment. At baseline there were no differences between the groups in terms of body mass index, age, acne severity and hormone concentrations. Results showed that both treatments demonstrated effectiveness but that women treated with azelaic acid presented a better sleep quality after the treatment compared to baseline and to the group treated with the combined oral contraceptive. The combined oral contraceptive group presented an increase in cortisol and a decrease in free testosterone concentration in relation to baseline. These data suggest that both azelaic acid and combined oral contraceptive are effective in the treatment of adult female acne but, azelaic acid seems to be a more suitable option for those women who may benefit from a better subjective sleep quality.