Hemidesmus indicus induces apoptosis via proteasome inhibition and generation of reactive oxygen species.

Proteasome inhibition represents an important anticancer strategy. Here, we studied the mechanisms at the basis of the pro-apoptotic activity of the standardized decoction of Hemidesmus indicus, a plant evoking a complex anticancer activity, and explored its inhibition of proteasome activity in human leukemia cells. Additionally, we preliminary tested the cytotoxicity of some H. indicus's phytochemicals on leukemia cells and their intestinal absorption on a human intestinal epithelium model consisting of a monolayer of differentiated Caco2 cells. We observed a potent antileukemic effect for H. indicus, imputable to the modulation of different critical targets at protein and mRNA levels and the reduction of the 26S proteasome expression. We found that some phytomarkers of H. indicus decoction passed through the enterocyte monolayer. Overall, our study supports the pharmacological potential of H. indicus, which can represent an interesting botanical drug in the oncological area

Cancer stem cells and nanomedicine: new opportunities to combat multidrug resistance?

‘Multidrug resistance’ (MDR) is a difficult challenge for cancer treatment. The combined role of cytochrome P450 enzymes (CYPs) and active efflux transporters (AETs) in cancer cells appears relevant in inducing MDR. Chemotherapeutic drugs can be substrates of both CYPs and AETs and CYP inducers or inhibitors can produce the same effects on AETs. In addition, a small subpopulation of cancer stem-like cells (CSCs) appears to survive conventional chemotherapy, leading to recurrent disease. Natural products appear efficacious against CSCs; their combinational treatments with standard chemotherapy are promising for cancer eradication, in particular when supported by nanotechnologies

Dopamine-sensitive adenylyl cyclases in neuronal development: physiopathological and pharmacological implications.

Pharmacological studies on molecular mechanisms leading the differentiation of neurons with retained dopaminergic fate and function are claimed for treatment of neurodegenerative disorders, such as Parkinson’s disease and schizophrenia. This goal could be achieved by neuronal replacement therapies based upon the manipulation of endogenous precursors in situ or by transplantation-based approaches. Signals conveyed by the adenylyl cyclase pathway seem crucial for a suitable differentiation of neurons. Therefore, dopamine-sensitive isoforms of adenylyl cyclase are here considered as key cues for dopaminergic neuronal patterning and so as interesting therapeutic targets to induce regenerative processes or drive correct neuronal development

A structural investigation on poly(glycolic acid)

Powder X-ray diffraction patterns were recorded of the orthorhombic form of poly(glycolic acid) and the peak profiles were investigated in order to obtain the best fit with proposed structural models. The optimized unit cell parameters are in a good agreement with those reported from fibre X-ray diffraction patterns; moreover, the peak analysis allowed to evaluate the average crystallite dimensions along the three main crystallographic directions and in particular to observe a smaller size along the c axis. The R factors indicating the agreement between calculated and experimental patterns are satisfactory. © 1992

Properties of ion channels in the protoplasts of the Mediterranean seagrass Posidonia oceanica

Posidonia oceanica (L) Delile, a seagrass endemic of the Mediterranean sea, provides food and shelter to marine organisms. As environment contamination and variation in physico-chemical parameters may compromise the survival of the few Posidonia genotypes living in the Mediterranean, comprehending the molecular mechanisms controlling Posidonia growth and development is increasingly important. In the present study the properties of ion channels in P. oceanica plasma membranes studied by the patch-clamp technique in protoplasts obtained from the young non-photosynthetic leaves were investigated. In protoplasts that were presumably originated from sheath cells surrounding the vascular bundles of the leaves, an outwardrectifying time-dependent channel with a single channel conductance of 58 \ub1 2 pS which did not inactivate, was selective for potassium and impermeable to monovalent cations such as Na +, Li + and Cs + was identified. In the same protoplasts, an inward-rectifying channel that has a timedependent component with single channel conductance of the order of 10 pS, a marked selectivity for potassium and no permeation to sodium was also identified, as was a third type of channel that did not display any ionic selectivity and was reversibly inhibited by tetraethylammonium and lanthanum. A comparison of Posidonia channel characteristics with channels identified in terrestrial plants and other halophytic plants is included

Estrogens metabolites in the release of inflammatory mediators from human amnion-derived cells

Aims: Human amnion-derived cells have been used as in vitro model to test the release of inflammatory mediators, such as arachidonic acid (AA) and prostaglandin E2 (PGE2). We compared estrogen metabolites for their ability to induce AA release, to influence PGE2 production and to interact toward intracellular estrogen receptors (ERs). Main methods: Metabolites effects on AA and PGE2 release were examined by radiolabelled substrate incorporation and by colorimetric enzyme immunoassays, respectively. [3H]17-beta-estradiol binding displacements were performed on Ro-20-1724 treated whole cells. Key findings: In WISH cells, estrone, 2-hydroxy-estrone and estriol induced a rapid dose dependent release of AA that was not inhibited by cycloheximide. Estrone and 2-hydroxy-estrone showed biphasic dose-response curves of PGE2, whereas estriol and 16-alpha-hydroxy-estrone increased PGE2 levels at high concentrations. 2-methoxy-estrone, 4-hydroxy-estradiol and 4-hydroxy-estrone did not significantly affected PGE2 release. 2-methoxy–estradiol and 2-hydroxy-estradiol decreased the PGE2 release. Effects of metabolites on PGE2 were inhibited by cycloheximide and by the ERs antagonist tamoxifen. In AV3 cells PGE2 production was poorly detectable. On Ro-20-1724 treated WISH cells the Ki of 17-beta-estradiol was 29.2 +/- 5.4 nM. Estrone, 2-methoxy-estrone and 2-methoxy-estradiol showed similar affinity values. The hydroxyl substituent at position 2, 4 and 16 decreased or a markedly increased the affinity for estradiol or estrone derivatives, respectively. Significance: The estrogen metabolites induced nongenomic effects on AA release from WISH cells. The influences on PGE2 release were detectable only on WISH cells. These effects appeared genomic and mediated by intracellular ERs, whose properties seemed strongly dependent on intracellular cAMP levels

Fat and Water Photon Scattering Data for in vivo Lean and Fatty Tissue Composition Study

Photon scattering cross-section data for freshly excised and filtered liquid pig fat was measured in the interval χ = 0.02 to 0.64 Å-1 (χ = E*[sin(θ/2)]/12.4; E being the photon incident energy (keV) and θ the scattering angle). The experimental results demonstrate that the marked intermolecular effects of coherent scattering in the forward direction can be exploited as a tool for characterizing lean and fatty tissue. Photon scattering cross-section data for freshly excised and filtered liquid pig fat was measured in the interval χ = 0.02 to 0.64 angstroms (χ = E*[sin(θ/2)]/12.4; E being the photon incident energy (keV) and θ the scattering angle). The experimental results demonstrate that the marked intermolecular effects of coherent scattering in the forward direction can be exploited as a tool for characterizing lean and fatty tissue

Relationship between crystallization regimes and melting phenomena in isotactic polypropylene

A study has been made of the relationship between crystallization regimes and multiple peaks in the melting endotherms of isotactic polypropylene (iPP). Some samples of this polymer can show multiple melting peaks in differential scanning calorimetry (DSC) scans: this phenomenon has been studied and associated with a regime III of crystallization, giving rise to a phase which appears disordered from a crystallographic point of view. During melting, this phase recrystallizes, giving a more ordered phase which melts at a higher temperature. On the contrary, crystallization in regime II produces a crystalline phase which melts with a single endotherm. These phenomena have been studied by DSC, by optical microscopy in polarized light and by X-ray diffraction; the results are discussed in terms of the proposed interpretation