From flesh to soul : the dichotomy of the body in Alfonso Varano, Salomone Fiorentino, And Giacomo Leopardi

This thesis advocates the existence of a sub-cluster in late eighteenth- and early nineteenth-century Italian poetry, often imperfectly labelled as ‘sepulchral’, focusing on the co-existence between the physicality of death, as explored by coeval science, and the religious longing for eternal life. By dynamically relying on Dante’s model, these texts explore the tension between belief and secularisation characterising the Enlightenment age, embodied by the corpse as an object of supreme ‘abjection’ and, at the same time, of devotional contemplation. Moreover, my thesis hypothesises the existence of a direct literary lineage running from the works of Alfonso Varano (particularly Visioni sacre e morali, 1789) and Salomone Fiorentino (Fiorentino’s Elegie di S. F. in morte di Laura sua moglie, 1790) to Giacomo Leopardi’s early poetic experiments, and particularly to his youthful, Dante-inspired poem Appressamento della morte (1816). As a consequence, I detect a so-far under-investigated strain in Italy’s literary history, enabling me to provide a different assessment of Leopardi’s sources in composing this poem, beyond its overt Dantean inspiration

Recent Progress in Photoresponsive Biomaterials

: Photoresponsive biomaterials have garnered increasing attention recently due to their ability to dynamically regulate biological interactions and cellular behaviors in response to light. This review provides an overview of recent advances in the design, synthesis, and applications of photoresponsive biomaterials, including photochromic molecules, photocleavable linkers, and photoreactive polymers. We highlight the various approaches used to control the photoresponsive behavior of these materials, including modulation of light intensity, wavelength, and duration. Additionally, we discuss the applications of photoresponsive biomaterials in various fields, including drug delivery, tissue engineering, biosensing, and optical storage. A selection of significant cutting-edge articles collected in recent years has been discussed based on the structural pattern and light-responsive performance, focusing mainly on the photoactivity of azobenzene, hydrazone, diarylethenes, and spiropyrans, and the design of smart materials as the most targeted and desirable application. Overall, this review highlights the potential of photoresponsive biomaterials to enable spatiotemporal control of biological processes and opens up exciting opportunities for developing advanced biomaterials with enhanced functionality

Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?

Abstract: Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin’s efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis

Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: in vitro and in vivo anti-tumor activity

Multiple myeloma (MM) cells induce relevant angiogenic effects within the human bone marrow milieu (huBMM) by the aberrant expression of angiogenic factors. Hypoxia triggers angiogenic events within the huBMM and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is over-expressed by MM cells. Since synthetic miR-199a-5p mimics negatively regulates HIF-1α, we here investigated a miRNA-based therapeutic strategy against hypoxic MM cells. We indeed found that enforced expression of miR-199a-5p led to down-modulated expression of HIF-1α as well as of other pro-angiogenic factors such as VEGF-A, IL-8, and FGFb in hypoxic MM cells in vitro. Moreover, miR-199a-5p negatively affected MM cells migration, while it increased the adhesion of MM cells to bone marrow stromal cells (BMSCs) in hypoxic conditions. Furthermore, transfection of MM cells with miR-199a-5p significantly impaired also endothelial cells migration and down-regulated the expression of endothelial adhesion molecules such as VCAM-1 and ICAM-1. Finally, we identified a hypoxia\AKT/miR-199a-5p loop as a potential molecular mechanism responsible of miR-199a-5p down-regulation in hypoxic MM cells. Taken together our results indicate that miR-199a-5p has an important role for the pathogenesis of MM and support the hypothesis that targeting angiogenesis via a miRNA/HIF-1α pathway may represent a novel potential therapeutical approach for this still lethal diseas

The small molecule SI113 synergizes with mitotic spindle poisons in arresting the growth of human glioblastoma multiforme

Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM therapy often fails to ensure control of a disease characterized by high frequency of recurrences and progression. In search for novel therapeutic approaches, we assayed the effect of compounds from a cancer drug library on the ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle poisons. Our previous work showed that the effectiveness of the spindle poison paclitaxel in inhibiting cancer cell growth was dependent on the expression of RANBP1, a regulatory target of the serine/threonine kinase SGK1. Recently, we developed the small molecule SI113 to inhibit SGK1 activity. Therefore, we explored the outcome of the association between SI113 and selected spindle poisons, finding that these drugs generated a synergistic cytotoxic effect in GBM cells, drastically reducing their viability and clonogenic capabilities in vitro, as well as inhibiting tumor growth in vivo. We also defined the molecular bases of such a synergistic effect. Because SI113 displays low systemic toxicity, yet strong activity in potentiating the effect of radiotherapy in GBM cells, we believe that this drug could be a strong candidate for clinical trials, with the aim to add it to the current GBM therapeutic approaches

24 Gliflozins and ventricular function in patients affected by chronic heart failure with diabetes mellitus

Abstract Aims Diabetes is the most common comorbidity of HF patients. SGLT2 inhibitors has been shown to reduce hospitalization in patients with HF. The cardioprotective mechanisms of gliflozines have not been elucidated. The aim of our study was to evaluate the effect of SGLT2 inhibitors on right and left ventricular function in T2DM patients with HF. Methods and results One hundred and fifteen consecutive outpatients with CHF and T2DM were screened in the Daunia Heart Failure Registry. Seventy-eight of them were enrolled and followed up between May 2019 and September 2020. All patients underwent conventional, TDI and strain echocardiography in an ambulatory setting, at the beginning and after 3 months of therapy with SGLT2 inhibitors. Seventy-eight consecutive outpatients with CHF and T2DM (mean age 67.4 ± 8.4 years, male: 83%) were enrolled in the study. Thirty-eight of them started the treatment with SGLT2 inhibitors, while the remaining forty continued their original therapy. After 3 months of therapy, LVEF, LVEDD, and LVESD statistically improved (respectively, from 39.68 ± 7.78% to 45.08 ± 9.04%, P: 0.001 and 57.32 ± 9.76 mm to 54.16 ± 6.54 mm, P: 0.01 and from 47.51 ± 1.58 mm to 43.24 ± 8.12, P: 0.0008). Changes in left ventricular function and dimensions were not significant in patients who did not started a therapy with SGLT2 inhibitors. There was a statistically significant reduction of E/E′ (from 16.51 ± 22.55 to 9.73 ± 3.35, P: 0.0007) in patients with treatment with SGLT2i. Moreover, there was an improvement of right ventricular function, due to a statistically significant reduction of PAPs and increase of TAPSE (respectively, from 30.63 ± 8.80 to 24.00 ± 8.35, P: 0.008; from 19.16 ± 2.54 to 21.18 ± 2.84, P: 0.0003) and S′ (10.42 ± 2.09 to 12.91 ± 2.50, P: 0.000) 3 months after the administration of SGLT2 inhibitors therapy vs. the control group. Conclusions In a real-world scenario, our results showed that the treatment with SGLT-2 inhibitors in patients with CHF and diabetes is associated with an echocardiographic biventricular function improvement

Development of a New Tool for 3D Modeling for Regenerative Medicine

The effectiveness of therapeutic treatment based on regenerative medicine for degenerative diseases (i.e., neurodegenerative or cardiac diseases) requires tools allowing the visualization and analysis of the three-dimensional (3D) distribution of target drugs within the tissue. Here, we present a new computational procedure able to overcome the limitations of visual analysis emerging by the examination of a molecular signal within images of serial tissue/organ sections by using the conventional techniques. Together with the 3D anatomical reconstitution of the tissue/organ, our framework allows the detection of signals of different origins (e.g., marked generic molecules, colorimetric, or fluorimetric substrates for enzymes; microRNA; recombinant protein). Remarkably, the application does not require the employment of specific tracking reagents for the imaging analysis. We report two different representative applications: the first shows the reconstruction of a 3D model of mouse brain with the analysis of the distribution of the β-Galactosidase, the second shows the reconstruction of a 3D mouse heart with the measurement of the cardiac volume

Contribution to the ecology of the Italian hare (Lepus corsicanus)

the italian hare (Lepus corsicanus) is endemic to Central-Southern Italy and Sicily, classified as vulnerable due to habitat alterations, low density and fragmented populations and ecological competition with the sympatric european hare (Lepus europaeus). Despite this status, only few and local studies have explored its ecological features. We provided some key traits of the ecological niche of the italian hare as well as its potential distribution in the italian peninsula. All data derived from genetically validated presences. We generated a habitat suitability model using maximum entropy distribution model for the italian hare and its main competitor, the european hare. the dietary habits were obtained for the italian hare with DnA metabarcoding and High-throughput Sequencing on faecal pellets. The most relevant environmental variables affecting the potential distribution of the italian hare are shared with the european hare, suggesting a potential competition. the variation in the observed altitudinal distribution is statistically significant between the two species.The diet of the Italian hare all year around includes 344 plant taxa accounted by 62 families. The Fagaceae, Fabaceae, Poaceae, Rosaceae and Solanaceae (counts > 20,000) represented the 90.22% of the total diet. Fabaceae (60.70%) and Fagaceae (67.47%) were the most abundant plant items occurring in the Spring/Summer and Autumn/Winter diets, respectively. the Spring/Summer diet showed richness (N = 266) and diversity index values (Shannon: 2.329, Evenness: 0.03858, Equitability: 0.4169) higher than the Autumn/Winter diet (N = 199, Shannon: 1.818, Evenness: 0.03096, Equitability: 0.3435). Our contribution adds important information to broaden the knowledge on the environmental (spatial and trophic) requirements of the Italian hare, representing effective support for fitting management actions in conservation planning

Genetic variants associated with gastrointestinal symptoms in Fabry disease.

Gastrointestinal symptoms (GIS) are often among the earliest presenting events in Fabry disease (FD), an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A. Despite recent advances in clinical and molecular characterization of FD, the pathophysiology of the GIS is still poorly understood. To shed light either on differential clinical presentation or on intervariability of GIS in FD, we genotyped 1936 genetic markers across 231 genes that encode for drug-metabolizing enzymes and drug transport proteins in 49 FD patients, using the DMET Plus platform. All nine single nucleotide polymorphisms (SNPs) mapped within four genes showed statistically significant differences in genotype frequencies between FD patients who experienced GIS and patients without GIS: ABCB11 (odd ratio (OR) = 18.07, P = 0,0019; OR = 8.21, P = 0,0083; OR=8.21, P = 0,0083; OR = 8.21, P = 0,0083),SLCO1B1 (OR = 9.23, P = 0,0065; OR = 5.08, P = 0,0289; OR = 8.21, P = 0,0083), NR1I3 (OR = 5.40, P = 0,0191) and ABCC5 (OR = 14.44, P = 0,0060). This is the first study that investigates the relationships between genetic heterogeneity in drug absorption, distribution, metabolism and excretion (ADME) related genes and GIS in FD. Our findings provide a novel genetic variant framework which warrants further investigation for precision medicine in FD

A 17-Gene Expression Signature for Early Identification of Poor Prognosis in Clear Cell Renal Cell Carcinoma

: The Identification of reliable Biomarkers able to predict the outcome after nephrectomy of patients with clear cell renal cell carcinoma (ccRCC) is an unmet need. The gene expression analysis in tumor tissues represents a promising tool for better stratification of ccRCC subtypes and patients' evaluation. Methods: In our study we retrospectively analyzed using Next-Generation expression analysis (NanoString), the expression of a gene panel in tumor tissue from 46 consecutive patients treated with nephrectomy for non-metastatic ccRCC at two Italian Oncological Centres. Significant differences in expression levels of selected genes was sought. Additionally, we performed a univariate and a multivariate analysis on overall survival according to Cox regression model. Results: A 17-gene expression signature of patients with a recurrence-free survival (RFS) < 1 year (unfavorable genomic signature (UGS)) and of patients with a RFS > 5 years (favorable genomic signature (FGS)) was identified and resulted in being significantly correlated with overall survival of the patients included in this analysis (HR 51.37, p < 0.0001). Conclusions: The identified Genomic Signatures may serve as potential biomarkers for prognosis prediction of non-metastatic RCC and could drive both follow-up and treatment personalization in RCC management