Exploring pathways for sustained melanogenesis in facial melasma: an immunofluorescence study.

BACKGROUND: The physiopathology of epidermal hypermelanization in melasma is not completely understood. Several cytokines and growth factors are increased in skin with melasma, nevertheless, nor the pathways involved in the increased αMSH expression have been adequately evaluated, nor a model for sustained focal melanogenesis is available. OBJECTIVE: To explore stimulatory pathways for epidermal pigmentation in facial melasma related to αMSH: those linked to ultraviolet radiation, oxidative stress, inflammation, neural crest pigmentation cell differentiation and antagonism of αMSH. METHODS: Paired skin biopsies (3 mm) from 26 women with facial melasma and from normal adjacent skin (<2 cm far) were processed for immunofluorescence with markers for p53, p38, αMSH, MC1R, Melan-A, IL-1α, COX2, Wnt1, WIF-1 and ASIP. RESULTS: The fluorescence intensity in the skin from melasma was higher for MC1R, αMSH at epidermis as at melanocytes (P < 0.05). There were no differences between the sites in epidermal protein expression of COX2, IL-1α, p53, WIF-1 and ASIP (P > 0.1). P53 was expressed only in epidermis, without difference between sites (P = 0.92). WNT1 was remarkable in the epidermis of melasma (P < 0.01), but not in dermis. Positive p38 cells were prominent in the upper dermis of melasma (P < 0.01), despite no marking in epidermis. CONCLUSION: Melanogenesis in melasma involves epithelial secretion of αMSH and activation of the Wnt pathway; nevertheless, it seems to be independent of the stimulation by ultraviolet radiation/p53, IL-1α, COX2/PgE2 , WIF-1 and ASIP. Damaged cells at upper dermis suggest the role of senescence/autophagy in sustained pigmentation in melasma.

Structure-activity relationship, molecular docking, and molecular dynamic studies of diterpenes from marine natural products with anti-HIV activity.

HIV-1 infection is a global epidemic whose treatment is limited majorly by viral resistance and adverse effects. Natural products from algae have been studied for many years, including antiviral, being an alternative to anti-HIV drug design. Since the isolation of natural products can be a hurdle, molecular modeling is an important tool to study these compounds. Herein, structure-activity relationship, molecular docking, and molecular dynamic studies were performed to direct the studies of ten marine natural products with anti-HIV activity. In the structure-activity relationship, descriptors were identified associating the anti-HIV activity of five diterpenes with possible action on the reverse transcriptase allosteric site. These diterpenes were evaluated by molecular docking, and it was identified that only dolabelladienetriol interacted in the allosteric site. Molecular dynamics suggested that the dolabelladienetriol might interfere with the viral RNA binding to HIV-1 RT by inducing a conformational change of the enzyme. Also, in silico ADMET simulations predicts that the dolabelladienetriol present a high potential to be successfully developed as a drug. Thus, applying in silico approaches was possible to suggest potential anti-HIV compounds derived from marine natural products.Communicated by Ramaswamy H. Sarma.

Experimental cryptorchidism enhances testicular susceptibility to dibutyl phthalate or acrylamide in Sprague-Dawley rats.

Cryptorchidism (CPT), the most common male congenital abnormality, is variably associated with other male reproductive tract problems. We evaluated if cryptorchid rats develop enhanced testicular susceptibility to dibutyl phthalate (DBP) or acrylamide (AA) after extended exposure. Three studies with rats were performed: (1) in utero and postnatal exposure to DBP or AA; (2) establishment of CPT and orchiopexy; and (3) in utero and postnatal exposures to DBP or AA associated with CPT/orchiopexy. Seminiferous tubules were histologically scored according to the severity of lesions: (1) Rats exposed to DBP (score 1.5) or AA (score 1.1) presented mostly preserved spermatogenesis. Some seminiferous tubules showed vacuolated germinative epithelium, germ cell apoptosis, and a Sertoli cell-only (SCO) pattern. (2) CPT (score 3.3) resulted in decreased absolute testes weights, degenerated and SCO tubules, and spermatogenesis arrest that were reversed by orchiopexy (score 1.1). (3) Exposure to DBP or AA with CPT/orchiopexy led to atrophic testes, spermatogenesis arrest, germ cell exfoliation/multinucleation, and SCO tubules (both chemicals score 2.5). Exposure to chemicals such as DBP or AA prevented the recovery of cryptorchid testes by orchiopexy. The possible role of environmental contaminants should be considered when looking for factors that modulate human testicular disorders associated with CPT.