Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage

Aminosalicylates, corticosteroids and immunosuppressants are currently the therapeutic choices in inflammatory bowel diseases (IBD), however, with limited remission and often serious side effects. Meanwhile complementary and alternative medicine (CAM) use is increasing, particularly herbal medicine. Boswellia serrata is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest for its usefulness in IBDs. The mechanism of this pharmacological potential of Boswellia serrata was investigated in colonic epithelial cell monolayers exposed to H2O2 or INF-\u3b3+TNF-\u3b1, chosen as in vitro experimental model of intestinal inflammation. The barrier function was evaluated by the transepithelial electrical resistance (TEER) and paracellular permeability assay, and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin) immunofluorescence. The expression of phosphorylated NF-\u3baB and reactive oxygen species (ROS) generation were determined by immunoblot and cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE) and its pure derivative acetyl-11-keto-\u3b2-boswellic acid (AKBA), were tested at 0.1-10 \u3bcg/ml and 0.027\u3bcg/ml, respectively. BSE and AKBA safety was demonstrated by no alteration of intestinal cell viability and barrier function and integrity biomarkers. H2O2 or INF-\u3b3+TNF-\u3b1 treatment of Caco-2 cell monolayers significantly reduced TEER, increased paracellular permeability and caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA pretreatment significantly prevented functional and morphological alterations and also the NF-\u3baB phosphorylation induced by the inflammatory stimuli. At the same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2 exposure. Data showed the positive correlation of the antioxidant activity with the mechanism involved in the physiologic maintenance of the integrity and function of the intestinal epithelium. This study elucidates the pharmacological mechanisms mediated by BSE, in protecting intestinal epithelial barrier from inflammatory damage and supports its use as safe adjuvant in patients affected by IBD

Analysis of inter-fraction setup errors and organ motion by daily kilovoltage cone beam computed tomography in intensity modulated radiotherapy of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Intensity-modulated radiotherapy (IMRT) enables a better conformality to the target while sparing the surrounding normal tissues and potentially allows to increase the dose to the target, if this is precisely and accurately determined. The goal of this work is to determine inter-fraction setup errors and prostate motion in IMRT for localized prostate cancer, guided by daily kilovoltage cone beam computed tomography (kVCBCT).</p> <p>Methods</p> <p>Systematic and random components of the shifts were retrospectively evaluated by comparing two matching modalities (automatic bone and manual soft-tissue) between each of the 641 daily kVCBCTs (18 patients) and the planning kVCT. A simulated Adaptive Radiation Therapy (ART) protocol using the average of the first 5 kVCBCTs was tested by non-parametric bootstrapping procedure.</p> <p>Results</p> <p>Shifts were < 1 mm in left-right (LR) and in supero-inferior (SI) direction. In antero-posterior (AP) direction systematic prostate motion (2.7 ± 0.7 mm) gave the major contribution to the variability of results; the averages of the absolute total shifts were significantly larger in anterior (6.3 ± 0.2 mm) than in posterior (3.9 mm ± 0.2 mm) direction. The ART protocol would reduce margins in LR, SI and anterior but not in posterior direction.</p> <p>Conclusions</p> <p>The online soft-tissue correction based on daily kVCBCT during IMRT of prostate cancer is fast and efficient. The large random movements of prostate respect to bony anatomy, especially in the AP direction, where anisotropic margins are needed, suggest that daily kVCBCT is at the present time preferable for high dose and high gradients IMRT prostate treatments.</p

Assessment of Parathyroid Function in Clinical Practice: Which Parathyroid Hormone Assay Is Better?

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Chemistry at the protein-mineral interface in L-ferritin assists the assembly of a functional (μ3-oxo)Tris[(μ2-peroxo)] triiron(III) cluster

X-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (μ3-oxo)Tris[(μ2-peroxo)(μ2-glutamato-κO:κO′)](glutamato-κO)(diaquo)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin