La guerra civile immaginata. Un dilemma dell'Italia repubblicana

Il periodo repubblicano è un periodo di molte tensioni anche violente ma non di guerra civile. Il saggio ragiona sul perché, viceversa, in situazioni politicamente importanti quest'espressione sia stata utilizzat

Cladosporols A and B, two natural peroxisome proliferator-activated receptor gamma (PPARγ) agonists, inhibit adipogenesis in 3 T3-L1 preadipocytes and cause a conditioned-culture-medium-dependent arrest of HT-29 cell proliferation

Background: Obesity and type 2 diabetes mellitus, which are widespread throughout the world, require therapeutic interventions targeted to solve clinical problems (insulin resistance, hyperglycaemia, dyslipidaemia and steatosis). Several natural compounds are now part of the therapeutic repertoire developed to better manage these pathological conditions. Cladosporols, secondary metabolites from the fungus Cladosporium tenuissimum, have been characterised for their ability to control cell proliferation in human colon cancer cell lines through peroxisome proliferator-activated receptor gamma (PPAR\u3b3)-mediated modulation of gene expression. Here, we report data concerning the ability of cladosporols to regulate the differentiation of murine 3T3-L1 preadipocytes. Methods: Cell counting and MTT assay were used for analysing cell proliferation. RT-PCR and Western blotting assays were performed to evaluate differentiation marker expression. Cell migration was analysed by wound-healing assay. Results: We showed that cladosporol A and B inhibited the storage of lipids in 3T3-L1 mature adipocytes, while their administration did not affect the proliferative ability of preadipocytes. Moreover, both cladosporols downregulated mRNA and protein levels of early (C/EBP\u3b1 and PPAR\u3b3) and late (aP2, LPL, FASN, GLUT-4, adiponectin and leptin) differentiation markers of adipogenesis. Finally, we found that proliferation and migration of HT-29 colorectal cancer cells were inhibited by conditioned medium from cladosporol-treated 3T3-L1 cells compared with the preadipocyte conditioned medium. Conclusions: To our knowledge, this is the first report describing that cladosporols inhibit in vitro adipogenesis and through this inhibition may interfere with HT-29 cancer cell growth and migration. General significance: Cladosporols are promising tools to inhibit concomitantly adipogenesis and control colon cancer initiation and progression

Tissue expression of Squamous Cellular Carcinoma Antigen (SCCA) is inversely correlated to tumor size in HCC

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate squamous cellular carcinoma antigen (SCCA) in serum and in tumoral and paired peritumoral tissues. We studied 27 patients with liver cirrhosis (LC) and 55 with HCC: 20 with a single nodule < 3 cm (s-HCC) and 35 with a single nodule > 3 cm or multifocal (l-HCC).</p> <p>Methods</p> <p>Serum SCCA was measured by the ELISA kit, and in frozen tissues by immunohistochemistry, quantified with appropriate imaging analysis software and expressed in square microns. Continuous variables are reported as means and 95% confidence intervals. Comparisons between independent groups were performed with a generalized linear model and Tukey grouping. Pearson's correlation coefficients were determined to evaluate relations between markers. Qualitative variables were summarized as count and percentage. Statistical significance was set at p-value < 0.05.</p> <p>Results</p> <p>Serum SCCA values in LC patients were 0.41 (0.31–0.55) ng/ml and statistically different from both HCC groups: 1.6 (1.0–2.6) ng/ml in s-HCC, 2.2 (1.28–2.74) ng/ml in l-HCC. SCCA in hepatic tissue was 263.8 (176.6–394.01) μm²in LC patients, statistically different from values in s-HCC: 1163.2 (863.6–1566.8) μm²and l-HCC: 625.8 (534.5–732.6). All pairwise comparisons between groups yielded statistically significant differences. Tumoral SCCA resulted linearly related with nodule size, showing a statistically significant inverse relation between the two variables (b = -0.099, p = 0.024).</p> <p>Conclusion</p> <p>There was no statistically significant correlation between tissue and serum levels of SCCA. The significantly stronger expression of SCCA in smaller compared to larger HCC could be important for early HCC detection. However, the increased expression in peritumoral tissue could affect the significance of serological detection.</p

Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer

Backgound: The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far. Methods: To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry. Results: Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide -514 and - 262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples. Conclusions: Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC

An evaluation of coronary atherosclerosis using coronary CT in subjects with asymptomatic carotid lesions.

The evaluation of coronary lesions in patients with asymptomatic carotid plaque represents a very promising line of research to assess cardiovascular risk and the possible implementation of a more aggressive prevention therapy. METHODS: In this study we enrolled 102 patients with intermediate to high cardiovascular risk but no history of coronary artery disease. The first group, consisting of 51 patients, underwent a Coronary CT scan (CCT-group) as well as carotid ultrasonography. The second group, also consisting of 51 patients, underwent coronary angiography (CA) and carotid ultrasonography. RESULTS: The absence of a statistically significant difference between the involvement of both coronary and carotid sites, assessed by CCT and CA, confirms the role of coronary CT as a useful method in the preclinical evaluation of cardiovascular risk. In the CCT group, the correlation between atherosclerosis of carotid artery and coronary disease, as well as between the mean carotid intimal medial thickness and the number of involved coronary vessels, and between the maximum values of carotid plaque and the presence of coronary artery stenosis > 50%, were statistically significant. The Agatson calcium score was also statistically associated with carotid plaque size. CONCLUSION: The imaging biomarkers have a key role in the evaluation of subclinical atherosclerotic disease. Moreover, carotid ultrasound examination and a CT-scan of coronary arteries, in a particular sub-group of patients with intermediate to high cardiovascular risk, can play a crucial role to assess the preventive therapeutic strategies

Obesity and iron deficiency anemia as risk factors for asymptomatic bacteriur

Background: Few studies examined the risk factors of asymptomatic bacteriuria, showing contradictory results. Our study aimed to examine the association between different clinical and laboratory parameters and asymptomatic bacteriuria in internal medicine patients. Materials and methods: 330 consecutive hospitalized subjects, asymptomatic for urinary tract infections (UTIs), underwent to microscopic examination of urine specimens. 100 subjects were positive for microscopic bacteriuria and were recruited into the study. At the quantitative urine culture 31 subjects of study population were positive while 69 subjects were negative for bacteriuria. Results: The analysis of clinical characteristics showed that the two groups of subjects (positive and negative urine culture for bacteriuria) were significant different (p b 0.05) about obesity (76.7% vs 42% respectively), metabolic syndrome (80.6% vs 44,9%), cholelithiasis (35.5% vs 13,2%) and iron deficiency anemia (80.6% vs 53,6%). The univariate analysis showed that only obesity, cholelithiasis and iron deficiency anemia were positively associated with positive urine culture for bacteriuria (Odds Ratios [OR] = 3.79, p = 0.0003; OR = 2,65, p =0.0091; OR = 2.63, p = 0.0097; respectively). However, the multivariate analysis by logistic regression showed that only obesity and iron deficiency anemia, independently associated with positive urine culture for bacteriuria (OR = 3.9695, p = 0.0075; OR = 3.1569, p = 0.03420 respectively). Conclusions: This study shows that obesity and iron deficiency anemia are independent risk factors for asymptomatic bacteriuria

484. Preclinical Proof of Concept of Transcriptional Silencing and Replacement Strategy for Treatment of Retinitis Pigmentosa Due To RHODOPSIN Mutations

Silencing and replacement strategy is a promising approach to overcome mutational heterogeneity of genetic defects. In autosomal dominant retinitis pigmentosa (adRP) due to rhodopsin gene (RHO) approximately 200 different mutations have been described, posing a challenge for the design of effective therapeutics.We designed a silencing and replacement strategy based on transcriptional silencing through an artificial zinc finger DNA-binding protein lacking effector domains (ZF6DBD), and tested both efficacy and safety in two animal models.In a murine model of adRP, we show that AAV-mediate retinal delivery (AAV2/8-CMV-ZF6-DBD) is associated with selective transcriptional silencing of the human mutated allele resulting in morphological and functional (Electroretinography, ERG a-wave and b-wave responses) rescue. We then tested the effect of transcriptional silencing in the porcine large pre-clinical model. Delivery of a low dose (AAV2/8-CMV-ZF6-DBD, 1×10e10 vector genomes, vg) of the ZF6 transcriptional silencer to the porcine retina resulted in robust transcriptional silencing of the endogenous porcine RHO transcript. Cell sorting of transduced photoreceptors showed an almost complete RHO transcriptional silencing effect (90% RHO transcriptional repression), underscoring the potency of the system. To determine the safety of the zinc-finger silencer we performed extensive RNA-seq analysis on treated and control retinae. The data sets generated demonstrate selective RHO gene transcriptional repression and a remarkably low number of differential expressed genes (DEGs), supporting specificity and thus, safety. The co-administration to the porcine retina of the AAV-ZF6 silencer (AAV2/8-CMV-ZF6-DBD) and the AAV-RHO replacement (5×10e11 vg, AAV2/8-GNAT1-HumanRHO) constructs resulted in a balanced silencing and replacement effect. This data support the use of zinc-finger based RHO transcriptional silencing for the development of a clinical trial for adRP patients

Psychological Types and Learning Styles

The aim of the research is to measure the relations and the directions of two modalities to study the approach to objects and learning. An observation group of 213 subjects, 93 males (43,7%) and 120 females (56,3%), (average of 24,73 years old; SD 2,28) all students from the V year Medicine and Surgery from the University of Messina, were involved. The evaluation was carried out with The Kolb's LSI II (Italian Adaptation) and the Mayers-Bryggs Type Indicator. Descriptive and correlational analysis were carried out.  Significant correlations emerged respectful to the Jung's introversion and extraversion (Hp 1), so that we assist to a positive correlation among every style. Referring to Learning Styles and the Jung's functions (Hp 2), significant positive and negative correlations emerged, but for AE. Significant and negative correlations emerged for judging functions, AC and RO (Hp 3). Negative correlations were highlighted by the relation among the two Leaning Styles groups and judging functions (Hp 4). The study could provide an integrative way to consider the teaching activity and  the curricula . The relations suggest that the awareness of the students about their learning and adaptation process can provide a viable mode to satisfy their desires

320 transcriptional silencing via synthetic dna binding protein lacking canonical repressor domains as a potent tool to generate therapeutics

Transcription factors (TFs) function by the combined activity of their DNA-binding domains (DBDs) and effector domains (EDs). Here we show that in vivo delivery of an engineered DNA-binding protein uncoupled from the repressor domain entails complete and gene-specific transcriptional silencing. To silence RHODOPSIN (RHO) gain-of-function mutations, we engineered a synthetic DNA-binding protein lacking canonical repressor domains and targeted to the regulatory region of the RHO gene. AAV-mediate retinal delivery at a low dose (AAV2/8-CMV-ZF6-DBD, 1×10e10 vector genomes, vg) in the porcine retina resulted in selective transcriptional silencing of RHO expression. The rod photoreceptors (the RHO expressing cells) transduced cells when isolated by FACS-sorting showed the remarkable 90% RHO transcriptional repression. To evaluate genome-wide transcriptional specificity, we analyzed the porcine retina transcriptome by RNA sequencing (RNA-Seq). The differentially expressed genes (DEGs) analysis showed that only 19 genes were perturbed. In this study, we describe a system based on a synthetic DNA binding protein enabling targeted transcriptional silencing of the RHO gene by in vivo gene transfer. The high rate of transcriptional silencing occurring in transduced cells supports applications of this regulatory genomic interference with a synthetic trans-acting factor for diseases requiring gene silencing in a large number of affected cells, including for instance a number of neurodegeneration disorders. The result support a novel mode of gene targeted silencing with a DNA-binding protein lacking intrinsic activity