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

Validity Analysis of Wii Balance Board Versus Baropodometer Platform Using an Open Custom Integrated Application

Abstract Standing balance tests represent the most common way to assess person's functional ability and they were realized by means of specialized and expensive platforms, especially in clinicians' environments. Wii Balance Board (WBB) is video-game based device that measures center of pressure (CoP) oscillations and it showed promising performance compared with 'gold standard' force platforms. In this paper we propose an open integrated custom application to define balance outcomes using WBB. These outcomes were used to execute a validity analysis of WBB performance compared with baropodometer platform (BP). Ten subjects performed two standing balance tests with open and closed eyes respectively on WBB and BP in separate occasion. Validity analysis was carried out using r-Pearson correlation coefficient, ICC analysis, paired-sample t-Test and Bland-Altman plots. Results confirmed that the WBB, although has a fraction of cost of other platforms, represents a tool suitable for some clinician analysi

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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Unilateral condylar hyperplasia recurrence after orthognathic surgery: a case report

Introduction: Unilateral Condylar Hyperplasia (UCH) is an uncommon condition resulting in facial asymmetry and malocclusion. At the time of diagnosis, an accurate evaluation of condylar activity through bone SPECT is necessary to determine the most appropriate surgical treatment. The Authors present a case of a UCH recurrence after orthognathic surgery in order to discuss about the clinical role of condylar SPECT in UCH therapeutic management. Case report: A 60-years old female patient was referred to the Department of Maxillo-Facial Surgery of Sapienza University of Rome for a relapse of mandibular laterodeviation. At the age of 24, she underwent orthognathic surgery after a diagnosis of UCH without condylar SPECT evaluation. As part of our clinical routine, condylar SPECT was performed and a significant difference in radiotracer uptake (20%) was found between the left condylar region and the contralateral one. She underwent high condilectomy and Bilateral Mandibular Sagittal Osteotomy. She had no evidence of recurrence till today. Discussion: Optimal surgical management of UCH is still controversial. In the diagnostic phase of UCH, a functional evaluation of condylar growth status by bone SPECT is an essential step to avoid long-term recurrence of mandibular asymmetry. On the basis of condylar metabolic activity, UCH can be classified in an active phase or a stationary phase. Clinical and functional evaluation of patients with mandibular asymmetry should be standardized in order to plan the most appropriate surgical and orthodontic treatment

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

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Autocrine Regulation of IL-21 Production in Human T Lymphocytes

Abstract IL-21 has pathologic function in immune-inflammatory diseases. IL-21 mediates its functions through a heterodimeric receptor, composed of a specific subunit, termed IL-21R, and the common γ-chain. IL-21 is mostly produced by CD4+ T cells, but molecular mechanisms that regulate IL-21 synthesis are not fully understood. The fact that CD4+ T cells express high levels of IL-21R and are capable of functionally responding to IL-21 raises the possibility that IL-21 may regulate its own production. We here show that IL-21 enhances IL-21 RNA and protein expression in human peripheral blood CD3+ T cells in a dose- and time-dependent fashion. Additionally, both IL-7 and IL-15, but not IL-4, induce IL-21, thus suggesting that common γ-chain signals are not sufficient to promote IL-21 synthesis. Analysis of molecular mechanisms underlying IL-21 induction reveals that IL-21 activates Stat3 and enhances its recruitment to IL-21 gene promoter. Pharmacologic inhibition and knockdown of Stat3 by small interference RNA largely prevent IL-21 induction in IL-21-treated cells. Consistently, IL-21 is inducible in T cells by IL-6, another cytokine that activates Stat3. Finally, we show that IL-21 positively regulates its own expression in human intestinal CD3+ lamina propria lymphocytes, and blockade of endogenous IL-21 in cultures of CD3+ lamina propria lymphocytes isolated from patients with Crohn's disease, a chronic inflammatory bowel disease characterized by high IL-21, down-regulates Stat3 activation and IL-21 expression. These data suggest the existence of a positive autocrine loop that could help to amplify and stabilize IL-21-driven, T cell-mediated responses

Air–Sea Interaction in the Central Mediterranean Sea: Assessment of Reanalysis and Satellite Observations

Air–sea heat fluxes are essential climate variables, required for understanding air–sea interactions, local, regional and global climate, the hydrological cycle and atmospheric and oceanic circulation. In situ measurements of fluxes over the ocean are sparse and model reanalysis and satellite data can provide estimates at different scales. The accuracy of such estimates is therefore essential to obtain a reliable description of the occurring phenomena and changes. In this work, air–sea radiative fluxes derived from the SEVIRI sensor onboard the MSG satellite and from ERA5 reanalysis have been compared to direct high quality measurements performed over a complete annual cycle at the ENEA oceanographic observatory, near the island of Lampedusa in the Central Mediterranean Sea. Our analysis reveals that satellite derived products overestimate in situ direct observations of the downwelling short-wave (bias of 6.1 W/m2) and longwave (bias of 6.6 W/m2) irradiances. ERA5 reanalysis data show a negligible positive bias (+1.0 W/m2) for the shortwave irradiance and a large negative bias (−17 W/m2) for the longwave irradiance with respect to in situ observations. ERA5 meteorological variables, which are needed to calculate the air–sea heat flux using bulk formulae, have been compared with in situ measurements made at the oceanographic observatory. The two meteorological datasets show a very good agreement, with some underestimate of the wind speed by ERA5 for high wind conditions. We investigated the impact of different determinations of heat fluxes on the near surface sea temperature (1 m depth), as determined by calculations with a one-dimensional numerical model, the General Ocean Turbulence Model (GOTM). The sensitivity of the model to the different forcing was measured in terms of differences with respect to in situ temperature measurements made during the period under investigation. All simulations reproduced the true seasonal cycle and all high frequency variabilities. The best results on the overall seasonal cycle were obtained when using meteorological variables in the bulk formulae formulations used by the model itself. The derived overall annual net heat flux values were between +1.6 and 40.4 W/m2, depending on the used dataset. The large variability obtained with different datasets suggests that current determinations of the heat flux components and, in particular, of the longwave irradiance, need to be improved. The ENEA oceanographic observatory provides a complete, long-term, high resolution time series of high quality in situ observations. In the future, more similar sites worldwide will be needed for model and satellite validations and to improve the determination of the air–sea exchange and the understanding of related processes