Interleukin-23 and Th17 Cells in the Control of Gut Inflammation

Crohn's Disease and Ulcerative Colitis, the major forms of inflammatory bowel diseases (IBDs) in humans, have been traditionally associated with exaggerated and poorly controlled T helper (Th) type 1 or Th2 cell response, respectively. More recent studies have, however, shown that IBDs are also characterized by a sustained production of cytokines made by a distinct lineage of Th cells, termed Th17 cells. The demonstration that Th17-related cytokines cause pathology in many organs, including the gut, and that expansion and maintenance of Th17 cell responses require the activity of IL-23, a cytokine made in excess in the gut of IBD patients has contributed to elucidate new pathways of intestinal tissue damage as well as to design new therapeutic strategies. In this review, we discuss the available data supporting the role of the IL-23/Th17 axis in the modulation of intestinal tissue inflammation

Colorectal Cancer Chemoprevention by Mesalazine and Its Derivatives

Patients with inflammatory bowel disease (IBD) face an increased lifetime risk of developing colorectal cancer (CRC). Independent factors associated with increased risk include long disease duration, extensive colonic involvement, young age at onset of IBD, severity of inflammation, primary sclerosing cholangitis, backwash ileitis, and a family history of CRC, thus emphasising the role of intestinal inflammation as an underlying mechanism. This notion is also supported by the demonstration that the use of certain drugs used to attenuate the ongoing mucosal inflammation, such as mesalazine, seems to associate with a reduced incidence of colitis-associated CRC. In the last decade, work from many laboratories has contributed to delineate the mechanisms by which mesalazine alters CRC cell behaviour. In this paper, we review the available experimental data supporting the ability of mesalazine and its derivatives to interfere with intracellular signals involved in CRC cell growth

Interleukin-21 in cancer immunotherapy: Friend or foe?

Interleukin (IL)-21, a cytokine produced by activated conventional CD4+ T lymphocytes and Natural Killer T cells, drives anti-tumor immunity in the skin and kidney. However IL-21 is also pro-inflammatory in many tissues and promotes colitis-associated colon cancer. Understanding the biology of IL-21 in these different situations is needed to ensure maximal therapeutic benefit

A modified sentinel node and occult lesion localization (SNOLL) technique in non-palpable breast cancer. A pilot study

Background: The spread of mammographic screening programs has allowed an increasing amount of early breast cancer diagnosis. A modern approach to non-palpable breast lesions requires an accurate intraoperative localization, in order to achieve a complete surgical resection. In addiction, the assessment of lymph node status is mandatory as it represents a major prognostic factor in these patients. The aim of this study is to evaluate the reliability of a modified technical approach using a single nanocolloidal radiotracer to localize both sentinel node and breast occult lesion. Methods: Twenty-five patients with a single non-palpable breast lesions and clinically negative axilla were enrolled. In the same day of surgery, patients underwent intratumoral and peritumoral administration of 99mTc-labeled nanocolloid tracer under sonographic guidance. A lymphoscintigraphy was performed to localize the sentinel lymph node and its cutaneous projection was marked on the skin in order to guide the surgeon to an optimal incision. During surgery an hand-held gamma-detection probe was used to select the best surgical access route and to guide localization of both occult breast lesion and sentinel lymph node. After specimen excision, the surgical field was checked with the gamma-probe to verify the absence of residual sources of significant radioactivity, thereby ensuring a radical treatment in a single surgical session and minimizing normal tissue excision. Results: Both targeted breast lesion and sentinel lymph node were localized and removed at the first attempt in every patients and histopathological diagnosis of malignancy was confirmed in 25/26 samples. Non-palpable lesions were included within the surgical margins in all patients and in all samples surgical margins were free from neoplastic infiltration thus avoiding any further reintervention. Only two patients showed metastatic involvement of sentinel lymph node. Conclusions: The modified sentinel node and occult lesion localization (SNOLL) technique performed with a single injection of nanocolloidal radiotracer has shown an excellent intraoperative identification rate of both non-palpable lesion and sentinel lymph node. This procedure offers, as opposed to standard techniques, an accurate, simple and reliable approach to the management of non-palpable breast cancer

Aryl Hydrocarbon Receptor-Induced Signals Up-regulate IL-22 Production and Inhibit Inflammation in the Gastrointestinal Tract

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Tissue Inhibitor of Metalloproteinase-3 Regulates Inflammation in Human and Mouse Intestine

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Use of Kluyveromyces marxianus to Increase Free Monoterpenes and Aliphatic Esters in White Wines

An increasing interest in novel wine productions is focused on non-Saccharomyces yeasts due to their potential in improving sensory profiles. Although Kluyveromyces marxianus has been originally isolated from grapes and its enzymatic activities are used in oenology, rarely it has been used as co-starter. The K. marxianus Km L2009 strain has been characterized here and selected as a co-starter both at laboratory- and winery-scale fermentation. The Km L2009 strain showed growth of up to 40 (mg/L) of sulfites and 6% (v/v) of ethanol. Gas chromatographic analysis demonstrates that wines produced by mixed fermentation contain remarkably higher quantities of free monoterpenes and aliphatic esters than wines produced only by commercial strains of Saccharomyces cerevisiae. Differences in the volatile organic compound composition produced sensorially distinct wines. In light of these results, it is possible to state that even within the K. marxianus species it is possible to select strains capable of improving the aromatic quality of wines

Fabrication of deformable patient-specific AAA models by material casting techniques

BackgroundAbdominal Aortic Aneurysm (AAA) is a balloon-like dilatation that can be life-threatening if not treated. Fabricating patient-specific AAA models can be beneficial for in-vitro investigations of hemodynamics, as well as for pre-surgical planning and training, testing the effectiveness of different interventions, or developing new surgical procedures. The current direct additive manufacturing techniques cannot simultaneously ensure the flexibility and transparency of models required by some applications. Therefore, casting techniques are presented to overcome these limitations and make the manufactured models suitable for in-vitro hemodynamic investigations, such as particle image velocimetry (PIV) measurements or medical imaging.MethodsTwo complex patient-specific AAA geometries were considered, and the related 3D models were fabricated through material casting. In particular, two casting approaches, i.e. lost molds and lost core casting, were investigated and tested to manufacture the deformable AAA models. The manufactured models were acquired by magnetic resonance, computed tomography (CT), ultrasound imaging, and PIV. In particular, CT scans were segmented to generate a volumetric reconstruction for each manufactured model that was compared to a reference model to assess the accuracy of the manufacturing process.ResultsBoth lost molds and lost core casting techniques were successful in the manufacturing of the models. The lost molds casting allowed a high-level surface finish in the final 3D model. In this first case, the average signed distance between the manufactured model and the reference was (−0.2±0.2) mm. However, this approach was more expensive and time-consuming. On the other hand, the lost core casting was more affordable and allowed the reuse of the external molds to fabricate multiple copies of the same AAA model. In this second case, the average signed distance between the manufactured model and the reference was (0.1±0.6) mm. However, the final model’s surface finish quality was poorer compared to the model obtained by lost molds casting as the sealing of the outer molds was not as firm as the other casting technique.ConclusionsBoth lost molds and lost core casting techniques can be used for manufacturing patient-specific deformable AAA models suitable for hemodynamic investigations, including medical imaging and PIV