The Small Molecule BIBR1532 Exerts Potential Anti-cancer Activities in Preclinical Models of Feline Oral Squamous Cell Carcinoma Through Inhibition of Telomerase Activity and Down-Regulation of TERT

Expression of telomerase reverse transcriptase (TERT) and telomerase activity (TA) is a main feature of cancer, contributing to cell immortalization by causing telomeres dysfunction. BIBR1532 is a potent telomerase inhibitor that showed potential anti-tumor activities in several types of cancer, by triggering replicative senescence and apoptosis. In a previous work, we detected, for the first time, TERT expression and TA in preclinical models of feline oral squamous cell carcinoma (FOSCC); therefore, we aimed at extending our investigation by testing the effects of treatment with BIBR1532, in order to explore the role of telomerase in this tumor and foreshadow the possibility of it being considered as a future therapeutic target. In the present study, treatment of FOSCC cell lines SCCF1, SCCF2, and SCCF3 with BIBR1532 resulted in successful inhibition of TA, with subsequent cell growth stoppage and decrease in cell viability. Molecular data showed that up-regulation of cell cycle inhibitor p21, unbalancing of Bax/Bcl-2 ratio, and down-regulation of survival gene Survivin were mostly involved in the observed cellular events. Moreover, BIBR1532 diminished the expression of TERT and its transcriptional activator cMyc, resulting in the down-regulation of epidermal growth factor receptor (EGFR), phospho-ERK/ERK ratio, and matrix metalloproteinases (MMPs)-1/-2 and−9, likely as a consequence of an impairment of TERT extra-telomeric functions. Taken together, our data suggest that BIBR1532 exerts multiple anti-cancer activities in FOSCC by inhibiting telomerase pathway and interfering with signaling routes involved in cell proliferation, cell survival, and invasion, paving the way for future translational studies aimed at evaluating its possible employment in the treatment of this severe tumor of cats

Chaunocephalus ferox (Digenea: Echinostomatidae) infection associated with fatal cachexia in a white stork (Ciconia ciconia)

Abstract Post-mortem examination of a sub-adult debilitated white stork (Ciconia ciconia) from southern Italy showed nodular enteritis associated with massive infection by Chaunocephalus ferox (Digenea: Echinostomatidae). Pathological changes included lesions ranging from traumatic destruction of tissues with hemorrhages and thickness of mucosa and submucosa at fluke penetration site to loss of duodenal villi and necrosis. Lesions through the whole intestinal tract associated with the digenean infection were considered as compatible with causing the cachexia and death of the white stork

The occurrence and pathogenicity of Serratospiculum tendo (Nematoda: Diplotriaenoidea) in birds of prey from southern Italy

The air sacs of free-ranging birds of prey (n¼652) from southern Italy, including 11 species of Accipitriformes and six of Falconiforms, were examined for infections with Serratospiculum tendo (Nematoda: Diplotriaenoidea). Of the 17 species of birds examined, 25 of 31 (80.6%) peregrine falcons (Falco peregrinus) from Calabria Region and a single northern goshawk (Accipiter gentilis) from Campania Region were infected with S. tendo, suggesting a strong host specificity for the peregrine falcon. The northern goshawk and 18 of 25 infected peregrine falcons showed cachexia and all infected birds had bone fractures. At gross examination, air sacculitis and pneumonia were the most common lesions in infected birds. Microscopically, the air-sac walls showed thickening of the smooth muscle cells, resulting in a papillary appearance, along with hyperplasia of the mesothelium and epithelium, and foci of plasma cell infiltration and macrophages associated with several embryonated eggs and adult parasites. Extensive areas of inflammation were found in the lungs, characterized by lymphocytes, macrophages and fibroblasts surrounding embryonated eggs. The northern goshawk also had detachment of the dextral lung with several necrotic foci. In this case, the death of the bird was directly attributed to S. tendo infection. Lesions and pathological changes observed here suggest that S. tendo can cause disease

Pathology and molecular analysis of ' Hapalotrema mistroides ' (Digenea: Spirorchiidae) infecting a Mediterranean loggerhead turtle ' Caretta caretta '

Turtle blood flukes belonging to the family Spirorchiidae (Digenea) represent a major threat for sea turtle health and are considered the most important parasitic cause of turtle stranding and mortality worldwide. Despite the large diversity of spirorchiid species found globally, there are only 2 records for free-ranging Mediterranean sea turtles that date back to the late 1800s involving just Hapalotrema mistroides Monticelli, 1896. This study describes the first fatal confirmed case of spirorchiidiasis in a free-ranging Mediterranean loggerhead turtle Caretta caretta (Linnaeus) and, owing to the complexities of taxonomic identification of these parasites, provides the first molecular characterization and phylogenetic analysis of H. mistroides from the Mediterranean Sea. The loggerhead turtle showed cachexia and digestive disorders associated with severe damage to the pancreas and intestinal ganglia, caused by deposition of Hapalotrema eggs forming granulomas. Massive Hapalotrema egg emboli in several tissues and organs and encephalitis were the most probable contributions to the death of the turtle. The congruence between the phylogenetic analysis of both the ITS2 and 28S rDNA resolved the Italian and USA H. mistroides as the same species, confirming the parasite identification. The case here described clearly indicates that the blood flukes should be considered in the differential diagnosis of Mediterranean sea turtle diseases

Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes.

OBJECTIVE: Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disease characterized by medullary thyroid carcinoma (MTC) associated (MEN 2A and 2B) or not familial MTC (FMTC) with other endocrine neoplasia due to germline RET gene mutations. The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population. METHODS: We collected data on germline RET mutations of 250 families with hereditary MTC followed in 20 different Italian centres. RESULTS AND CONCLUSIONS: The most frequent RET amino acid substitution was Val804Met (19.6%) followed by Cys634Arg (13.6%). A total of 40 different germline RET mutations were present. Six families (2.4%) were negative for germline RET mutations. The comparison of the prevalence of RET germline mutations in the present study with those published by other European studies showed a higher prevalence of Val804Met and Ser891Ala mutations and a lower prevalence of Leu790Phe and Tyr791Phe (P<0.0001). A statistically significant higher prevalence of mutations affecting non-cysteine codons was also found (P<0.0001). Furthermore, the phenotype data collection showed an unexpected higher prevalence of FMTC (57.6%) with respect to other MEN 2 syndromes (34% MEN 2A and 6.8% of MEN 2B). In conclusion, we observed a statistically significant different pattern of RET mutations in Italian MEN 2 families with respect to other European studies and a higher prevalence of FMTC phenotype. The different ethnic origins of the patients and the particular attention given to analysing apparently sporadic MTC for RET germline mutations may explain these findings

Senegalese Migrtants in Italy: Beyond the Assimilation/Transnationalism Divide

The article is subdivided into three parts. The first provides readers with an overview of contemporary Senegalese \u201cculture of migration\u201d and explores how it translates into the Italian experience of West African immigration. In the second part, drawing on our and other colleagues\u2019 empirical work, we discuss the diversification of Senegalese strategies to enter Italian public space and to strengthen transnational connections with the context of origin. In the final part, we take into account the experiences of the \u201csecond generation\u201d and the engagement with projects facilitating the return of the elderly. We conclude by urging researchers to go beyond the assimilation versus transnationalism dichotomy to enhance our understanding of West African transnational migration into Southern Europe

Imagining greener pastures? Shifting perceptions of Europe and mobility in Senegalese society.

Over the past few years, the European crisis and the EU enforcement and externalization of border control have shaped how Europe and migration are perceived in Africa. Areas of out-migration, such as Senegal, are not only experiencing changes in mobility patterns but also a social diversification in the way in which \uabEurope\ubb is viewed and talked about. While several studies have underlined transformations occurring over time amongst Senegalese migrants in Europe, less attention has been paid to analysing their migration decisionmaking practices through a diachronic perspective. Drawing on ethnographic research carried out in Senegal and Italy between the mid-1990s and the first decade of the 2000s, this paper aims to explore how imaginaries and narratives of migration and destination countries are formed. Taking into account the interconnections of global and local dynamics, the paper discusses shifting perceptions of Europe and mobility in Senegal, highlighting how imaginaries of \uabelsewhere\ubb are ambivalent and historically grounde

Circadian rhythm of plasma renin activity

In this work the circadian rhythm of plasma renin activity was evaluate