Several effects of boron are induced by uncoupling steroid hormones from their transporters in blood.

Boron is increasingly added to food supplements due to multiple effects that have been reported in mammals after boric acid administration. Among these effects are inflammatory process control, bone and muscle strength enhancement, protein expression regulation, and a decreased risk of developing some pathologies in which these processes are key, such as osteoporosis, dermatological inflammatory non-infectious maladies and diseases affecting the central nervous system. Experimental data have suggested that steroid hormone levels in plasma change after boric acid administration, but a clear mechanism behind these variations has not been established. We analyzed possibilities for these changes and hypothesized that boric acid disrupts the interactions between steroid hormones and several carriers in plasma. In particular, we proposed that there is an uncoupling of the interactions between sex hormone binding globulin (SHBG) and estrogens and testosterone and that there are alterations in the binding of hydrophobic ligands by other carrier proteins in plasma. Further experimental and computational studies are required to support the hypothesis that boric acid and probably other boron-containing compounds can displace steroid hormones from their plasma carriers. If such phenomena are confirmed, boron administration with a clear mechanism could be employed as a therapeutic agent in several diseases or physiological events that require modulation of steroid hormone levels in plasma.

Selection of a GPER1 Ligand via Ligand-based Virtual Screening Coupled to Molecular Dynamics Simulations and Its Anti-proliferative Effects on Breast Cancer Cells.

BACKGROUND: Recent reports have demonstrated the role of the G Protein-Coupled Estrogen Receptor 1 (GPER1) on the proliferation of breast cancer. The coupling of GPER1 to estrogen triggers cellular signaling pathways related to cell proliferation. OBJECTIVE: Develop new therapeutic strategies against breast cancer. METHOD: We performed in silico studies to explore the binding mechanism of a set of G15 /G1 analogue compounds. We included a carboxyl group instead of the acetyl group from G1 to form amides with several moieties to increase affinity on GPER1. The designed ligands were submitted to ligand-based and structure-based virtual screening to get insights into the binding mechanism of the best designed compound and phenol red on GPER1. RESULTS: According to the in silico studies, the best molecule was named G1-PABA ((3aS,4R,9bR)-4-(6- bromobenzo[d][1,3]dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-carboxylic acid). It was synthesized and assayed in vitro in breast cancer (MCF-7 and MDA-MB-231) and normal (MCF-10A) cell lines. Experimental studies showed that the target compound was able to decrease cell proliferation, IC50 values of 15.93 µM, 52.92 µM and 32.45 µM in the MCF-7, MDA-MB-231 and MCF-10A cell lines, respectively, after 72 h of treatment. The compound showed better IC50 values without phenol red, suggesting that phenol red interfere with the G1-PABA action at GPER1, as observed through in silico studies, which is present in MCF-7 cells according to PCR studies and explains the cell proliferation effects. CONCLUSION: Concentration-dependent inhibition of cell proliferation occurred with G1-PABA in the assayed cell lines and could be due to its action on GPER1.

Predicting peptide vaccine candidates against H1N1 influenza virus through theoretical approaches.

Identification of potential epitopes that might activate the immune system has been facilitated by the employment of algorithms that use experimental data as templates. However, in order to prove the affinity and the map of interactions between the receptor (major histocompatibility complex, MHC, or T-cell receptor) and the potential epitope, further computational studies are required. Docking and molecular dynamics (MDs) simulations have been an effective source of generating structural information at molecular level in immunology. Herein, in order to provide a detailed understanding of the origins of epitope recognition and to select the best peptide candidate to develop an epitope-based vaccine, docking and MDs simulations in combination with MMGBSA free energy calculations and per-residue free energy decomposition were performed, taking as starting complexes those formed between four designed epitopes (P1-P4) from hemagglutinin (HA) of the H1N1 influenza virus and MHC-II anchored in POPC membrane. Our results revealed that the energetic contributions of individual amino acids within the pMHC-II complexes are mainly dictated by van der Waals interactions and the nonpolar part of solvation energy, whereas the electrostatic interactions corresponding to hydrogen bonds and salt bridges determine the binding specificity, being the most favorable interactions formed between p4 and MHC-II. Then, P1-P4 epitopes were synthesized and tested experimentally to compare theoretical and experimental results. Experimental results show that P4 elicited the highest strong humoral immune response to HA of the H1N1 and may induce antibodies that are cross-reactive to other influenza subtypes, suggesting that it could be a good candidate for the development of a peptide-based vaccine.