Molecular Alterations in Gastric Preneoplastic Lesions and Early Gastric Cancer

Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa’s cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete (MUC2) and incomplete (MUC2, MUC5AC, and MUC6) intestinal metaplasia, gastric dysplasia/intra-epithelial neoplasia, and early gastric cancer. In particular, considering preinvasive neoplasia and early gastric cancer, some studies have demonstrated a correlation between molecular alterations and prognosis, for example, mucins phenotype in gastric dysplasia, and GATA6, TP53 mutation/LOH and MUC6 in early gastric cancer. Moreover, this review considers novelties from the literature regarding the (immuno)histochemical characterization of diffuse-type/signet ring cell gastric cancer, with particular attention to clinical outcomes of patients. The aim of this review is the evaluation of the state of the art regarding suitable biomarkers used in the pre-surgical phase, which can distinguish patients with different prognoses and help decide the best therapeutic strategy.     

Fluorescence Polarization Immunoassay for Rapid, Accurate and Sensitive Determination of Ochratoxin A in Wheat

A sensitive and accurate fluorescence polarization (FP) immunoassay has been developed for the determination of ochratoxin A (OTA) in naturally contaminated wheat samples. A fluorescein-labeled OTA tracer was synthesized, and its binding response with three monoclonal antibodies was tested. The most sensitive competitive FP immunoassay showed an IC₅₀ value of 0.48 ng/mL with a negligible cross-reactivity for ochratoxin B (1.7 %) and no cross-reactivity with other mycotoxins commonly occurring in wheat. The wheat sample was extracted with acetonitrile/water (60:40, v/v) and purified by a rapid solid-phase extraction procedure using an aminopropyl column prior to the FP immunoassay. The overall time of analysis was less than 20 min. The average recovery from spiked wheat samples (3 to 10 μg/kg) was 87 %, with relative standard deviations generally lower than 6 %. Limits of detection and quantification were 0.8 and 2.0 μg/kg, respectively. The trueness of the method was assessed by using two reference materials for OTA showing good accuracy and precision. A good correlation (r?=?0.995) was observed between OTA contamination of 19 naturally contaminated wheat samples analyzed by both FP immunoassay and high-performance liquid chromatography/immunoaffinity clean-up used as reference method. These results show that the developed FP method is suitable for high-throughput screening, as well as for reliable quantitative determination of OTA in wheat at level far below the EU regulatory limits.     

Animal models are reliably mimicking human diseases? A morphological study that compares animal with human NAFLD

Non‐alcoholic fatty liver disease (NAFLD) is a clinical‐pathological syndrome that includes a wide spectrum of morphological alterations. In research, animal models are crucial in evaluating not only the pathogenesis of NAFLD and its progression, but also the therapeutic effects of various agents. Investigations on the ultrastructural features of NAFLD in humans are not copious, due to the difficulty to obtain human samples and to the long time of NAFLD to evolve. Translational comparative studies on the reliability of animal models in representing the histopathologic picture as seen in humans are missing. To overcome this lack of investigations, we compared the ultrastructural NAFLD features of an animal model versus human. Sprague‐Dawley rats were fed with a high fat diet (HFD) for 1–4 weeks, while control rats were fed with a standard diet. Human specimens were collected from patients with diagnosed fatty liver disease, undergoing liver biopsies or surgery. Rat and human samples were examined by light microscopy and by transmission and high resolution scanning electron microscopy. The present work demonstrated that NAFLD in animal model and in human, share overlapping ultrastructural features. In conclusion, animal HFD represent an appropriate tool in studying the pathogenesis of NAFLD. Microsc. Res. Tech. 77:790–796, 2014. © 2014 Wiley Periodicals, Inc.     

Prebiotic effect of soluble fibres from modern and old durum-type wheat varieties on Lactobacillus and Bifidobacterium strains

BACKGROUND: Wheat grains are a rich source of dietary fibres, particularly in the western human diet. Many of the health effects attributed to dietary fibres are believed to be related to their microbial fermentation in the gut. This study evaluated the ability of two potentially probiotic strains, Lactobacillus plantarum L12 and Bifidobacterium pseudocatenulatum B7003, to ferment soluble dietary fibres (SDFs) from modern and ancient durum‐type wheat grains. RESULTS: Fibre microbial utilisation was highly variable and dependent on the strain. SDFs from the varieties Svevo and Solex supported the growth of L. plantarum L12 the best, whereas those from the varieties Anco Marzio, Solex and Kamut^® Khorasan were good carbohydrate substrates for B. pseudocatenulatum B7003. The highest prebiotic activity scores (describing the extent to which prebiotics support selective growth of probiotics) for B7003 were obtained with SDFs from the varieties Solex (0.57), Kamut^® Khorasan (0.56) and Iride (0.55), whereas for L12 the highest scores were achieved with the varieties Orobel (0.63), Kamut^® Khorasan (0.56) and Solex (0.53). CONCLUSION: The present study has identified some SDFs from durum‐type wheat grains as suitable prebiotic substrates for the selective proliferation of B. pseudocatenulatum B7003 and L. plantarum L12 in vitro. The results provide the basis for the potential utilisation of wheat‐based prebiotics as a component of synbiotic formulations. Copyright © 2012 Society of Chemical Industry     

The state of strain in single GaN nanocolumns as derived from micro-photoluminescence measurements

In the present paper, studies on the state of strain in single and ensembles of nanocolumns investigated by photoluminescence spectroscopy will be presented. The GaN nanocolumns were either grown in a bottom-up approach or prepared in a top-down approach by etching compact GaN layers grown on Si(111) and sapphire (0001) substrates. Experimental evidence for strain relaxation of the nanocolumns was found. The difference and development of the strain value for different nanocolumns could be verified by spatially resolved micro-photoluminescence on single nanocolumns separated from their substrate. A common D0X spectral position at 3.473 eV was found for all separated single GaN nanocolumns independent of the substrate or processing technique used, as expected for a relaxed system.     

Pathophysiology of Diverticular Disease: From Diverticula Formation to Symptom Generation

Diverticular disease is a common clinical problem, particularly in industrialized countries. In most cases, colonic diverticula remain asymptomatic throughout life and sometimes are found incidentally during colonic imaging in colorectal cancer screening programs in otherwise healthy subjects. Nonetheless, roughly 25% of patients bearing colonic diverticula develop clinical manifestations. Abdominal symptoms associated with diverticula in the absence of inflammation or complications are termed symptomatic uncomplicated diverticular disease (SUDD). The pathophysiology of diverticular disease as well as the mechanisms involved in the shift from an asymptomatic condition to a symptomatic one is still poorly understood. It is accepted that both genetic factors and environment, as well as intestinal microenvironment alterations, have a role in diverticula development and in the different phenotypic expressions of diverticular disease. In the present review, we will summarize the up-to-date knowledge on the pathophysiology of diverticula and their different clinical setting, including diverticulosis and SUDD.     

Characterizing bubble behavior in a pseudo-2D fluidized bed of wet particles

By applying digital image analysis on the bubble characteristics in a two dimensional wet-particle fluidized-bed, we report two-stage evolution of bubble characteristics with increasing liquid content. In the first stage, bubble number and uniformity of bubble fraction increase, while bubble average diameter and aspect ratio decrease. In the second stage, these characteristics shift toward an opposite direction. This two-stage evolution of bubble characteristics are analogous to that of reducing particle size in dry-particle fluidization, and the fluidizing properties of particles shifts from Geldart Group B to Group A and then to Group C. Furthermore, liquid addition causes a continuous decrease of bubble fraction and bubble flow rate. This is different from dry-particle fluidization, in which reducing particle size causes an increase trend. An explanation for this difference is that liquid addition increases the equivalent size of agglomerates in wet-particle fluidization, which is opposite to the effect of reducing particle size.     

Advanced Pyrrolidine-Carbamate Self-Immolative Spacer with Tertiary Amine Handle Induces Superfast Cyclative Drug Release

Amine-carbamate self-immolative (SI) spacers represent practical and versatile tools in targeted prodrugs, but their slow degradation mechanism limits drug activation at the site of disease. We engineered a pyrrolidine-carbamate SI spacer with a tertiary amine handle which strongly accelerates the spacer cyclization to give a bicyclic urea and the free hydroxy groups of either cytotoxic (Camptothecin) or immunostimulatory (Resiquimod) drugs. In silico conformational analysis and pK_a calculations suggest a plausible mechanism for the superior efficacy of the advanced SI spacer compared to state-of-art analogues.