Bioinformatics approaches applied to the discovery of antifungal peptides

Antifungal peptides (AFPs) comprise a group of substances with a broad spectrum of activities and complex action mechanisms. They develop in nature via an evolutionary process resulting from the interactions between hosts and pathogens. The AFP database is experimentally verified and curated from research articles, patents, and public databases. In this review, we compile information about the primary databases and bioinformatics tools that have been used in the discovery of AFPs during the last 15 years. We focus on the classification and prediction of AFPs using different physicochemical properties, such as polarity, hydrophobicity, hydrophilicity, mass, acidic, basic, and isoelectric indices, and other structural properties. Another method for discovering AFPs is the implementation of a peptidomic approach and bioinformatics filtering, which gave rise to a new family of peptides that exhibit a broad spectrum of antimicrobial activity against Candida albicans with low hemolytic effects. The application of machine intelligence in the sphere of biological sciences has led to the development of automated tools. The progress made in this area has also paved the way for producing new drugs more quickly and effectively. However, we also identified that further advancements are still needed to complete the AFP libraries

Clinical Application of Development of Nonantibiotic Macrolides That Correct Inflammation-Driven Immune Dysfunction in Inflammatory Skin Diseases

Background. Inflammation-driven immune dysfunction supports the development of several chronic human disorders including skin diseases. Nonantibiotic macrolides have anti-inflammatory and/or immunomodulatory activity that suggests the exploitation of these in the treatment of skin diseases characterized by inflammatory disorders. Materials and Methods. We performed an extensive review of the nonantibiotic macrolide literature published between 2005 and 2012, including cross-references of any retrieved articles. We also included some data from our own experience. Results. Calcineurin antagonists such as tacrolimus and ascomycins (e.g., pimecrolimus) act by inhibiting the activation of the nuclear factor for activated T cells (NFAT). There are new applications for these macrolides that have been available for several years and have been applied to skin and hair disorders such as atopic dermatitis, oral lichen planus, vitiligo, chronic autoimmune urticaria, rosacea, alopecia areata, pyoderma gangrenosum, Behcet’s disease, neutrophilic dermatosis, and lupus erythematosus. We also reviewed new macrolides, like rapamycin, everolimus, and temsirolimus. In addition to the literature review, we report a novel class of nonantibiotic 14-member macrocycle with anti-inflammatory and immunomodulatory effects. Conclusions. This paper summarizes the most important clinical studies and case reports dealing with the potential benefits of nonantibiotic macrolides which have opened new avenues in the development of anti-inflammatory strategies in the treatment of cutaneous disorders

Quantitative Proteomic Study Unmasks Fibrinogen Pathway in Polycystic Liver Disease

(1) Background: Polycystic liver disease (PLD) is a heterogeneous group of congenital disorders characterized by bile duct dilatation and cyst development derived from cholangiocytes. Nevertheless, the cystogenesis mechanism is currently unknown and the PLD treatment is limited to liver transplantation. Novel and efficient therapeutic approaches are th6us needed. In this context, the present work has a principal aim to find novel molecular pathways, as well as new therapeutic targets, involved in the hepatic cystogenesis process. (2) Methods: Quantitative proteomics based on SWATH–MS technology were performed comparing hepatic proteomes of Wild Type and mutant/polycystic livers in a polycystic kidney disease (PKD) murine model (Pkd1cond/cond;Tam-Cre−/+). (3) Results: We identified several proteins altered in abundance, with two-fold cut-off up-regulation or down-regulation and an adjusted p-value significantly related to hepatic cystogenesis. Then, we performed enrichment and a protein–protein analysis identifying a cluster focused on hepatic fibrinogens. Finally, we validated a selection of targets by RT-qPCR, Western blotting and immunohistochemistry, finding a high correlation with quantitative proteomics data and validating the fibrinogen complex. (4) Conclusions: This work identified a novel molecular pathway in cystic liver disease, highlighting the fibrinogen complex as a possible new therapeutic target for PLD

Biofilms and vulvovaginal candidiasis

Candida species, including C. albicans, are part of the mucosal flora of most healthy women, and inhabit the gastrointestinal and genitourinary tracts. Under favourable conditions, they can colonize the vulvovaginal mucosa, giving rise to symptomatic vulvovaginal candidiasis (VVC). The mechanism by which Candida spp. produces inflammation is unknown. Both, the blastoconidia and the pseudohyphae are capable of destroying the vaginal epithelium by direct invasion. Although the symptoms are not always related to the fungal burden, in general, VVC is associated with a greater number of yeasts and pseudohyphae. Some years ago, C. albicans was the species most frequently involved in the different forms of VVC. However, infections by different species have emerged during the last two decades producing an increase in causative species of VVC such as C. glabrata, C. parapsilosis, C. krusei and C. tropicalis. Candida species are pathogenic organisms that have two forms of development: planktonic and biofilm. A biofilm is defined as a community of microorganisms attached to a surface and encompassed by an extracellular matrix. This form of presentation gives microorganisms greater resistance to antifungal agents. This review, about Candia spp. with a special emphasis on Candida albicans discusses specific areas such as biofilm structure and development, cell morphology and biofilm formation, biofilm-associated gene expression, the cell surface and adherence, the extracellular matrix, biofilm metabolism, and biofilm drug resistance in vulvovaginitis biofilms as an important virulence factor in fungi