Beneficial effect of shikonin on experimental colitis induced by dextran sulfate sodium in Balb/C mice.

The naphthoquinone shikonin, a major component of the root of Lithospermum erythrorhizon, now is studied as an antiinflammatory agent in the treatment of ulcerative colitis (UC). Acute UC was induced in Balb/Cmice by oral administration of 5% dextran sodium sulfate (DSS). The disease activity index was evaluated, and a histologic study was carried out. Orally administered shikonin reduces induced UC in a dose-dependent manner, preventing the shortening of the colorectum and decreasing weight loss by 5% while improving the appearance of feces and preventing bloody stools. The disease activity index score was much lower in shikonin-treated mice than in the colitic group, as well as the myeloperoxidase activity. The expression of cyclooxygenase-2 was reduced by 75%, activation of NF-κB was reduced by 44%, and that of pSTAT-3 by 47%, as well as TNF-α, IL-1β, and IL-6 production. Similar results were obtained in primary macrophages culture. This is the first report of shikonin¿s ability to attenuate acute UC induced by DSS. Shikonin acts by blocking the activation of two major targets: NF-κB and STAT-3, and thus constitutes a promising potential therapeutic agent for the management of the inflammatory bowel disease

Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum

We have studied the effect of 5- O-demethylnobiletin ( 1) on both the inflammation of mouse ears induced by repeated application of 12- O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A (2) (PLA (2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity. Compound 1 reduced the oedema formation, cell infiltration, and tissue damage in the inflammation induced by TPA in mouse ears, along with the acute oedema induced by carrageenan in mouse paws and the acute PLA (2)-induced oedema in mouse paws. The flavone inhibited leukotriene B (4) formation in rat neutrophils and elastase release in human neutrophils, but did not reduce the expression of cyclooxygenase-2 (COX-2) in murine RAW 264.7 macrophages. These experimental results suggest that 1 may act through a direct inhibition of 5-LOX, without affecting the expression of COX-2

Identification of New Genetic Clusters in Glioblastoma Multiforme: EGFR Status and ADD3 Losses Influence Prognosis

Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. EGFR amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of EGFRvIII and FISH analysis for EGFR amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations between EGFR amplification and/or EGFRvIII, and SCNA in CDKN2A, MSH6, MTAP and ADD3. Interestingly, we found that both EGFRvIII and losses on ADD3 were independent markers of bad prognosis (p = 0.028 and 0.014, respectively). Finally, we got an unsupervised hierarchical classification that differentiated three clusters of patients based on their genetic alterations. It offered a landscape of EGFR co-alterations that may improve the comprehension of the mechanisms underlying GB aggressiveness. Our findings can help in defining different genetic profiles, which is necessary to develop new and different approaches in the management of our patients

Inhibition of the pro-inflammatory mediators’ production and anti-inflammatory effect of the iridoid scrovalentinoside

We have studied scrovalentinoside, an iridoid with anti-inflammatory properties isolated from Scrophularia auriculata ssp. pseudoauriculata, as an anti-inflammatory agent in different experimental models of delayed-type hypersensitivity. We found that scrovalentinoside reduced the edema induced by oxazolone at 0.5 mg/ear and sheep red blood cells at 10 mg/kg. The observed effect occurred during the last phase or inflammatory response; during the earlier phase or induction of the delayed-type hypersensitivity reaction, no significant activity was noted. Thus, scrovalentinoside reduced both the edema and cell infiltration in vivo and reduced lymphocyte proliferation in vitro, affecting the cycle principally during the first 48 h. Whereas cells stimulated with phytohemagglutinin changed from the G 0/G 1 phase to the S and G 2/M phases, when these same cells were treated with scrovalentinoside (100 μM), they remained in the G 0/G 1 phase. Finally, scrovalentinoside inhibited the production of the pro-inflammatory mediators’ TNF-α, IFN-γ, IL-1β, IL-2, IL-4, LTB 4, and NO, but had no effect on the production of the anti-inflammatory cytokine IL-10

Miocarditis de células gigantes: caso de evolución rápida y fatal.

La miocarditis de células gigantes (MCG) es una patología extremadamente infrecuente de origen desconocido y evolución fatal, que presenta histológicamente infiltrado inflamatorio miocárdico con presencia de células multinucleadas gigantes, sin apreciarse formación de granulomas. En el estudio inmunohistoquímico, las CGM expresan el marcador propio de la estirpe macrofágica CD68, siendo negativos para los marcadores musculares desmina y actina. La MCG se ha asociado a diversas entidades autoinmunes, infecciones virales, neoplasias y fármacos. Presentamos los resultados obtenidos de la necropsia realizada a un paciente de 55 años, que mostró de forma simultánea MCG, tiroiditis linfocitaria y mesotelioma pleural maligno, asociación no descrita hasta el momento en la literatura.Martínez Rodríguez, Miguel, [email protected] ; Ramos Soler, David, [email protected] ; Mayordomo Aranda, Empar, [email protected] ; Jordá Miñana, Ángela, [email protected] ; Cerda Nicolas, Jose Miguel, [email protected] ; Llombart Bosch, Antonio, [email protected]

Molecular Progression in Unusual Recurrent Non-Pediatric Intracranial Clear Cell Meningioma

We report a case of a recurrent clear cell meningioma (CCM) in the frontal lobe of the brain of a 67-year-old man. The patient developed three recurrences: at 3, 10, and 12 years after his initial surgery. Histopathology observations revealed a grade 2 CCM with positivity for vimentin and epithelial membrane antigen. Expression of E-cadherin was positive only in the primary tumour and in the first available recurrence. Fluorescence in situ hybridization analyses demonstrated 1p and 14q deletions within the last recurrence. Multiplex ligation-dependent probe amplification studies revealed a heterozygous partial NF2 gene deletion, which progressed to total loss in the last recurrence. The last recurrence showed homozygous deletions in CDKN2A and CDKN2B. The RASSF1 gene was hypermethylated during tumour evolution. In this report, we show the genetic alterations of a primary ccm and its recurrences to elucidate their relationships with the changes involved in the progression of this rare neoplasm