30 research outputs found

    Metabolic phenotype of bladder cancer

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    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1\u3b1]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-\u3b1-1,6-glucosidase, 4-\u3b1-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme serine hydroxymethyltransferase-2 (SHMT2), resulting in an increased glycine and purine ring of nucleotides synthesis, thus supporting cells proliferation. A deep understanding of the metabolic phenotype of bladder cancer will provide novel opportunities for targeted therapeutic strategies

    Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist

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    Objectives: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). Methods: The writing committee selected the HRCT criteria\ue2\u80\u94the Delphi items\ue2\u80\u94for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as \ue2\u80\u9cessential\ue2\u80\u9d, \ue2\u80\u9coptional\ue2\u80\u9d, or \ue2\u80\u9cnot relevant\ue2\u80\u9d. The items rated \ue2\u80\u9cessential\ue2\u80\u9d by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. Results: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated \ue2\u80\u9cessential\ue2\u80\u9d by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated \ue2\u80\u9cessential\ue2\u80\u9d by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. Conclusions: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists

    Smell and 3D Haptic Representation: A Common Pathway to Understand Brain Dynamics in a Cross-Modal Task. A Pilot OERP and fNIRS Study

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    Cross-modal perception allows olfactory information to integrate with other sensory modalities. Olfactory representations are processed by multisensory cortical pathways, where the aspects related to the haptic sensations are integrated. This complex reality allows the development of an integrated perception, where olfactory aspects compete with haptic and/or trigeminal activations. It is assumed that this integration involves both perceptive electrophysiological and metabolic/hemodynamic aspects, but there are no studies evaluating these activations in parallel. The aim of this study was to investigate brain dynamics during a cross-modal olfactory and haptic attention task, preceded by an exploratory session. The assessment of cross-modal dynamics was conducted through simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) recording, evaluating both electrophysiological and hemodynamic activities. The study consisted of two experimental sessions and was conducted with a sample of ten healthy subjects (mean age 25 5.2 years). In Session 1, the subjects were trained to manipulate 3D haptic models (HC) and to smell different scents (SC). In Session 2, the subjects were tested during an attentive olfactory task, in order to investigate the olfactory event-related potentials (OERP) N1 and late positive component (LPC), and EEG rhythms associated with fNIRS components (oxy- Hb and deoxy-Hb). The main results of this study highlighted, in Task 1, a higher fNIRS oxy-Hb response during SC and a positive correlation with the delta rhythm in the central and parietal EEG region of interest. In Session 2, the N1 OERP highlighted a greater amplitude in SC. A negative correlation was found in HC for the deoxy-Hb parietal with frontal and central N1, and for the oxy-Hb frontal with N1 in the frontal, central and parietal regions of interests (ROIs). A negative correlation was found in parietal LPC amplitude with central deoxy-Hb. The data suggest that cross-modal valence modifies the attentional olfactory response and that the dorsal cortical/metabolic pathways are involved in these responses. This can be considered as an important starting point for understanding integrated cognition, as the subject could perceive in an ecological context

    The State-Trait Anxiety Inventory: Shadows and Lights on its Construct Validity

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    Abstract Past studies on the factor validity of the Trait subscale of the Spielberger’s State-Trait Anxiety Inventory (STAI-T) do unanimously agree on its structure. In fact, researchers are still debating whether the STAI-T is unidimensional or multidimensional. Our aim was to clarify what the STAI-T measures. The STAI-T, the Beck Depression Inventory–II, the Teate Depression Inventory, and the Beck Anxiety Inventory were administered to 1124 psychiatric outpatients and to 877 healthy subjects. A confirmatory factor analysis was performed in order to compare various models in the literature. The internal consistency and convergent and discriminant validity of the STAI-T as well as its factorial subscales were assessed. The one-construct two-method (i.e., the STAI-T measures one substantive anxiety construct plus artifacts due to negative–positive item polarity) and the bifactor (i.e., the STAI-T comprises two first-order specific factors [“Anxiety” and “Depression”] and one first-order general factor) models were the best-fitting solutions for the STAI–T in both the clinical and nonclinical samples. The STAI–T total score correlated more strongly with measures of depression than with a concurrent measure of anxiety. The STAI-T should be considered a measure of general negative affect, including specific aspects of cognitive anxiety and depression together. Keywords Confirmatory factor analysis . Psychological tests . Anxiety . Depression . Reliability and validit

    Next Generation Sequencing ({NGS}) approach applied to species identification in mixed processed seafood products

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    Multi-species fish products are a growing market segment driven by several inputs, including urbanization, modern lifestyles and the availability of new technologies. These products are characterized by the absence of species-related morphological traits, as well as by the use of discards or fish waste as ingredients, that cannot be traced using a classical molecular approach. This historic inability to identify ingredients, coupled with a rather lean list of mandatory information required by current legislation, make these products the perfect target for substitution fraud. New molecular tools are now available to overcome this gap, such as the metabarcoding approach which can be used to trace species from complex food matrices. In this study, we used such an approach to sequence a fragment of 16S rRNA mitochondrial gene from 20 multispecies processed seafood products, sold on the Italian market and including breaded, burger and surimi, in order to evaluate mislabelling rates and formulate hypotheses regarding the potential drivers of fraudulent activities. Our results highlighted the presence of 120 marine taxa with an overall mislabelling rate of 45%, including some low-abundance taxa not included in the current Italian legislation, found mainly in the surimi samples. The presence of Tetraodontidae and swine DNA raise concerns regarding consumer safety and protection with regard to ethical or religious issues, as well the inclusion of undeclared molluscs potentially causing allergies. The high number of low-frequency taxa confirms the inclusion of discards and fish waste, doubtless positive for sustainable fisheries, but also boosting profits for the fish industry. Such practice, however, without an adequate labelling and traceability system, is a source of risk for consumers and marine ecosystems. In this context, a revision of national and international food safety legislation is needed; indeed, metabarcoding assessments can provide useful information to stakeholders and act as the future operational tool for inspective monitoring

    Species authentication of canned mackerel: Challenges in molecular identification and potential drivers of mislabelling

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    The market for canned mackerel is growing, due to their competitive price and to the excellent properties of the meat. However, the weak rules of current legislation, coupled with the loss of discrimination power due to being obliged to use short barcode regions, open up new challenges for traceability in processed products. In this study, for the first time, we applied a two-step mini-barcoding approach to identify canned mackerel sold in Italian markets and make assumptions on the potential drivers of mislabelling. Preliminary identification was performed using mini-barcode universal primers targeting a COI-fragment; then, in order to discriminate within the complex Scomber colias/S. japonicus/S. australasicus, we applied a second step, using new specific primers designed in the mitochondrial control region (D-loop). Comparison between labels and molecular identifications highlighted that the chance of mislabelling could be either 45% or 0%, depending on the interpretation of the generic terms used on the labels. Therefore, the study revealed that the ambiguous use, in the ingredient list, of ‘umbrella’ terms for naming fish species, such as ‘sgombro’ could be related to geographic origin of products and creates opportunities for fraudulent activities, but also misleads consumers. In light of this pattern, an urgent update of European legislation is needed to face current and future challenges for full chain traceability
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