The bovine pancreatic trypsin inhibitor (BPTI)-Kunitz-type protein ShPI-1 (UniProt: P31713) is the major protease inhibitor from the sea anemone Stichodactyla helianthus. This molecule is used in biotechnology and has biomedical potential related to its anti-parasitic effect. A pseudo wild-type variant, rShPI-1A, with additional residues at the N- and C-terminal, has a similar three-dimensional structure and comparable trypsin inhibition strength. Further insights into the structure-function relationship of rShPI-1A are required in order to obtain a better understanding of the mechanism of action of this sea anemone peptide. Using enzyme kinetics, we now investigated its activity against other serine proteases. Considering previous reports of bifunctional Kunitz-type proteins from anemones, we also studied the effect of rShPI-1A on voltage-gated potassium (Kv) channels. rShPI-1A binds Kv1.1, Kv1.2, and Kv1.6 channels with IC50 values in the nM range. Hence, ShPI-1 is the first member of the sea anemone type 2 potassium channel toxins family with tight-binding potency against several proteases and different Kv1 channels. In depth sequence analysis and structural comparison of ShPI-1 with similar protease inhibitors and Kv channel toxins showed apparent non-sequence conservation for known key residues. However, we detected two subtle patterns of coordinated amino acid substitutions flanking the conserved cysteine residues at the N- and C-terminal ends.

This study reports on the capacity of actinomycete strains isolated from Cuban soils to produce antifungal agents. The antimicrobial activities were determined by susceptibility disk assay methods. We isolated 563 different actinomycetes and 286 produced compounds with antifungal activity. Our screening method indicated the presence of many possible polyene macrolide antibiotics and the important antifungal activity in the soils rich in minerals.

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Eosinophilic gastroenteritis is a disease characterized histologically by an eosinophilic infiltration of the gut. The cause of this disease remains unclear, although both food allergy and food intolerance have been implicated in its pathogenesis. We report the case of a 22-year-old man in whom gastrointestinal symptoms first appeared in childhood, with involvement of mucosa and muscularis layers of stomach and bowel. He presented high IgE blood levels, and his prick test was positive to bovine, pig, and lamb sera. Immunoblots from calf, pig, and lamb sera, incubated with the patient's serum and revealed by autoradiography, demonstrated the presence of a 65-kDa protein band that was recognized by IgE antibodies but not by IgG. This band corresponded to bovine serum albumin, while IgE did not show reactivity with human albumin. These data suggest a possible role for IgE-mediated hypersensitivity mechanisms in the pathogenesis of eosinophilic gastroenteritis.

We report in this study the frequency of Streptomyces strains to produce macrolide‐lincosamide‐streptogramin (MLS) antibiotics isolated from Cuban soils. The screening assay is based on the induction of MLS‐resistance phenotype in a clinical isolated strain of Staphylococcus aureus S‐18. Our results suggest that of 800 Streptomyces strains isolated from different soil samples, 6% were positives in the screening test used. The ferralitic red soil from Pinar del Río (north) provided the major percentage (3·6%) of MLS producing strains. The other soil samples tested belonging to Guira de Melena and Bauta in Havana, Matanzas City, Topes De Collantes (Villa Clara), and Soroa Mountains (Pinar del Rio) hill reached very low percentages.

Protease inhibitors have been isolated from many variable sources; however, the need to identify and characterize new molecules has increased with the discovery of new therapeutic targets and the lack of specificity of already identified compounds with inhibitory activity. The goal of this work was to search for inhibitory activity against four proteolytic enzymes already recognized as therapeutic targets: human neutrophil elastase, dipeptidyl peptidase IV, subtilisin from Bacillus licheniformis and cathepsin K in selected marine invertebrates from the Caribbean Sea. A systematic screening was carried out with selected aqueous extracts belonging to 20 species from seven different phyla: Annelida, Bryozoa, Chordata, Cnidaria, Equinodermata, Mollusca and Porifera, all collected at the coast of Havana (Cuba). All extracts showing initial inhibitory activity were characterized in terms of IC50 values and specific inhibitory activity (SIA). Model enzymes were used in the case of human neutrophil elastase (porcine pancreatic elastase) and cathepsin K (papain) for the screening and all positive results were confirmed by testing toward the therapeutic targets. Ten extracts were identified showing inhibitory activity against human neutrophil elastase, for which the most promising values were obtained for Nerita peloronta. Only one extract, Bunodosoma granulifera, showed inhibitory activity against dipeptidyl peptidase IV with rather poor values of IC50 and SIA. Seven extracts showed inhibitory activity against B. licheniformis subtilisin with very good IC50 and SIA values for Lissodendorix isodyctialis, Cenchritis muricatus, and N. peloronta. Finally, eight extracts were positive for cathepsin K with almost similar parameters values among them. All these results confirmed the richness and potential of the marine invertebrate's fauna and indicated new promising sources for the identification of natural compounds with potential application in therapeutics.

Cytotoxic proteins and prodigiosin obtained from Serratia marcescens strains are known to induce tumor cell death, nevertheless its combination has not been studied. In this paper we evaluate the combined effects of these molecules in a panel of tumor cell lines. The results showed a marked inhibitory effect on the growth of tumor cell lines derived from tumors (i.e., melanoma) which are highly resistant to conventional anticancer drugs, while normal cells were less sensitive than tumor cells. TUNEL (TdT-mediated dUTP nick end labeling) and electrophoresis of HEp-2 cell DNA treated with MG2327 preparation [containing the P50 protein belonging to the serralysins and prodigiosin, from S. marcescens CMIB4202] showed a pattern of DNA fragments typically associated with apoptosis. Interestingly, prodigiosin enhanced by 1.6-fold the cytotoxic effect of P50 when acting in combination on HEp-2 cells. The broad cytotoxic activity of the combination on tumor cells as well as its selectivity open new frontiers in cancer therapy.