Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi-drug standard therapies often results in treatment failure and emergence of multi-drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe the ability of the exogenous AMP LLKKK18 to efficiently kill mycobacteria. The peptide's potential was boosted by loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity and degradability, while potentiating peptide targeting to main sites of infection. The nanogels were effectively internalized by macrophages and the peptide presence and co-localization with mycobacteria within host cells was confirmed. This resulted in a significant reduction of the mycobacterial load in macrophages infected in vitro with the opportunistic M. avium or the pathogenic M. tuberculosis, an effect accompanied by lowered pro-inflammatory cytokine levels (IL-6 and TNF-α). Remarkably, intra-tracheal administration of peptide-loaded nanogels significantly reduced infection levels in mice infected with M. avium or M. tuberculosis, after just 5 or 10 every other day administrations. Considering the reported low probability of resistance acquisition, these findings suggest a great potential of LLKKK18-loaded nanogels for TB therapeutics.

This work presents a newly developed formulation that holds great potential as a therapeutic approach for burn treatment. It is based on the sustained delivery of an antimicrobial peptide - LLKKK18 - from conjugates with dextrin, after degradation of dextrin backbone upon exposure to wound α-amylases. Conjugates were further embedded in Carbopol®, a commercially available hydrogel, suitable for topical administration and that provides a moist environment to the wound. Overall, we obtained an efficient, safe and non-expensive formulation that improves burn wound healing, maintains a moist environment within the wound, is easy to apply-and-remove, and has potential to prevent infection due to the presence of an antimicrobial peptide. Importantly, this is the first time the wound healing ability of LLKKK18 is demonstrated and that its main mechanisms of action are identified.

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Objectives: Breast cancer is an important health problem worldwide and the identification of prognostic markers in breast cancer is important in order to establish the most successful treatment for each patient. MiRNAs are non-coding RNAs, which modulate the expression of more than 50% of human genes at the post-transcriptional level. Deregulation of miRs is described in many types of tumors leading to their acting as tumor suppressors or oncogenes. This systematic review of the literature aimed to highlight tumor miRNA quantification, by real time PCR, as prognostic biomarkers in breast cancer. Methods: We systematically searched the PubMed database, in order to identify eligible studies and 1457 articles were initially selected. After reading the abstracts, 74 articles were read in complete and 20 studies were included in the review. Results: Twenty studies investigating the association between tumoral miRNA expression levels (predictive factors) and the prognostic in breast cancer patients were included in the review. MiRNA-21 and miRNA-200b were the most commonly investigated miRNA in breast cancer prognosis. Lymph node metastasis was significantly associated with the overexpression of miRNA-21, miRNA-301 and miRNA-370, and also to the under expression of miRNA-124, miRNA-127, miRNA-129-5p, miRNA199-5p, miRNA-206, miRNA-218, and miRNA-339-5. Distant metastasis was associated to miRNA-204 under expression. Tumor size was associated with the overexpression of miRNA-21 and miRNA-301, and also to under expression of miRNA-29b and miRNA129-5p. In relation to prognosis, lower survival rates were associated with the overexpression of miRNA-21, miRNA-301 and microRNA-711, and with under expression of miRNA-15a, miRNA-29b, miRNA-124, miRNA-129-5p, miRNA-199b-5p, miRNA-200b, miRNA-204, miRNA-206 and miRNA-218. Higher survival rates were associated with the overexpression of miRNA-339-5 and miRNA-127 On the other hand, higher survival rates were associated with overexpression of miRNA-339-5 and miRNA-127, and also to under expression of miRNA-210. Conclusion: According to the results, preclinical and clinical investigation performed on tissue-specific miRNAs can be considered as novel promising biomarkers for prediction of prognosis in breast cancer patients.