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A novel enzymatic platform for the sensing of H2O2 and glucose that uses L,L-diphenylalanine micro/nanostructures (FF-MNSs) as an enzyme support is shown. This platform is obtained by the self-assembly of poly(allylamine hydrochloride) (PAH), FF-MNSs, and microperoxidase-11 (MP11) anchored onto the peptide matrix, in two different crystal structures of FF-MNSs: hexagonal (P61) and orthorhombic (P22121). The electroactive area of the electrodes increases in the presence of FF-MNSs. We also demonstrate via theoretical calculations that the valence band energy of the orthorhombic structure allows it to be doped, similarly to p-type semiconductors, where PAH acts as a doping agent for the orthorhombic peptide structure, decreasing the band-gap by around 1 eV, which results in a smaller charge transfer resistance. These results are consistent with electrochemical impedance spectroscopy measurements, which further elucidate the role of the band structure of the orthorhombic FF-MNSs in the conductivity and electron transfer rates of the hybrid material. An effective communication between the electrode and the active site of a glucose oxidase enzyme through MP11-protein complexes occurs, paving the way for FF-MNSs in the orthorhombic phase for the future development of bioelectronics sensing devices.

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Peptide-based scaffolds are a frontier research area in materials science with widespread impact in biomedical engineering. In this paper, we describe a hybrid material formulated through the conjugation of electrospun polycaprolactone (PCL) fibers and micro/nanotubes of l,l-diphenylalanine (FF-MNTs). Morphology and crystallinity of the composite matrices are investigated using a wide range of analytical techniques including electron microscopy, thermal analyses, X-ray diffraction and micro-tomography. Peptide assemblies are found to produce deep modifications on the microstructure of PCL fibers, impacting average diameters, crystallinity degree and porous size in the polymer network. These changes are correlated with mechanical properties of the resulting scaffolds, whose strength is found to exhibit a brittle-to-ductile transition upon increasing the amount of FF-MNTs and lead to enhanced Young's moduli of polymer fibers. The PCL/FF-MNTs composites were tested for the drug delivery application of a lipophilic drug, benzocaine. In vitro permeation studies have shown that these polymer/peptide hybrids are able to produce a steady release of benzocaine over periods of up to ∼13 hours, much higher than commercially available gel formulations. Enzymatic tests have shown a significant increment in biodegradation rates in PCL/FF-MNTs hybrids containing higher peptide amounts, which exhibited almost 100% weight loss against only 10% found in pure PCL. Our findings indicate that using PCL/FF-MNTs materials is a simple route towards achieving enhanced mechanical strength of PCL networks that have the ability to promote controlled drug delivery from a completely biodegradable matrix.

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1. Twenty-two colorectal carcinomas were examined for the presence of estrogen (ER), progesterone (PR), androgen (AR) and glucocorticoid receptors (GR) by a charcoal dextran assay. 2. ER was detected in 4/13 (31%) and 5/9 (56%) of the rectum and colon carcinomas analyzed, and density values ranged from 10 to 14 and from 10 to 27 fm/mg protein, respectively. Normal distal or adjacent mucosa presented similar incidence and ER density values within the tumor ranges. 3. The incidence of PR-positive samples was also higher in colon than in rectal carcinomas (44% vs 23%). Normal mucosa displayed significantly higher PR titers than the corresponding tumor tissue. It seems reasonable to assume that normal colorectal mucosa may be one of the target tissues of progesterone activity. Most tumor biopsies and normal mucosa were completely AR negative, whilst GR was present in a larger fraction (63%) of tumoral specimens, occurring more commonly in colon than in rectum carcinomas. GR incidence tended to be higher in neoplasms than in normal mucosa (54% vs 38% in rectum and 78% vs 56% in colon), suggesting that glucocorticoids may be involved in the control of tumor-cell proliferation. 4. Our findings which indicate low densities of ER, PR, and absence of AR in some large bowel cancers, suggest sex hormone and endocrine independence for those cancers. The role of glucocorticoid receptors in those forms of cancer remains to be elucidated.

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1. Twenty-two colorectal carcinomas were examined for the presence of estrogen (ER), progesterone (PR), androgen (AR) and glucocorticoid receptors (GR) by a charcoal dextran assay. 2. ER was detected in 4/13 (31 per cent ) and 5/9 (56 per cent ) of the rectum and colon carcinomas analyzed, and density values ranged from 10 to 14 and from 10 to 27 fm/mg protein, respectively. Normal distal or adjacent mucosa presented similar incidence and ER density values within the tumor ranges. 3. The incidence of PR-positive samples was also higher in colon than in rectal carcinomas (44 per cent vs 23 per cent ). Normal mucosa displayed significantly higher PR titers than the corresponding tumor tissue. It seems reasonable to assume that normal colorectal mucosa may be one of the target tissues of progesterone activity. Most tumor biopsies and normal mucosa were completely AR negative, whilst GR was present in a larger fraction (63 per cent ) of tumoral specimens, occurring more commonly in colon than in rectum carcinomas. GR incidence tended to be higher in neoplasms than in normal mucosa (54 per cent vs 38 per cent in rectum and 78 per cent vs 56 per cent in colon), suggesting that glucocorticoids may be involved in the control of tumor-cell proliferation. 4. Our findings which indicate low densities of ER, PR, and absence of AR in some large bowel cancers, suggest sex hormone and endocrine independence for those cancers. The role of glucocorticoid receptors in those forms of cancer remains to be elucidated

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The effects of estradiol (E2), dihydrotestosterone (DHT) and dehydro-3-epiandrosterone (DHEA) on proliferation and progesterone receptor induction were studied in a breast cancer cell line (T47D) expressing estrogen, androgen, and progesterone receptors. A significant enhancement of growth and progesterone receptor expression was observed after treatment with E2 and DHEA, which was antagonized by the antiestrogen tamoxifen and not altered by the antiandrogen flutamide, supporting the involvement of estrogen receptors. When cells were treated with either E2 or DHEA, transforming growth factor-alpha mRNA was induced. DHT treatment did not alter growth but was effective in stimulating androgen receptors and down-regulating progesterone receptors.

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Characteristics of beta-adrenoceptors were analyzed using radioligand-binding techniques with 3H-dihydroalprenolol in lung specimens from 11 children with pulmonary hypertension (median age, three years) undergoing surgical repair of congenital heart defects and four pediatric control subjects (median age, five years) undergoing thoracotomy for removal of neoplasms or cysts. Scatchard analysis of 3H-DHA binding to lung membranes showed similar values of the dissociation constant in both groups (Kd = 0.72 +/- 0.22 nM in patients vs 1.22 +/- 0.22 nM in controls; p = NS). The receptor density was significantly increased in patients in comparison with controls, with respective values of 164 +/- 19 and 95 +/- 13 fmol/mg of protein (p less than 0.025), and correlated directly with mean pulmonary arterial pressure (r = 0.82; p less than 0.0005). No significant relationship was observed between receptor number and pulmonary arterial medial thickness. Thus, the increase in receptor density in these patients may be related to adaptative changes in cells other than vascular smooth muscle.

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