Saproxylic beetles of conservation interest in the Calabrian side of the Pollino National Park (Calabria, Italia): Lucanus tetraodon Thunberg, 1806, Osmoderma italicum Sparacio, 2000, Cerambyx cerdo Linnaeus, 1758 and Rosalia alpina (Linnaeus, 1758) (Coleoptera Lucanidae Cetoniidae Cerambycidae)

In this article an update on the distribution of Coleoptera Lucanus tetraodon Thunberg, 1806 (Lucanidae), Osmoderma italicum Sparacio, 2000 (Cetoniidae), Cerambyx cerdo Linnaeus, 1758 and Rosalia alpina (Linnaeus, 1758) (Cerambycidae) in the Calabrian side of the Pollino National Park is described. Data regarding the ecological part and the conservation status will be presented for each species. Therefore, of particular interest it can be noted: the presence in nine locations of L. tetraodon, an uncommon species and with little-known distribution; the discreet diffusion of O. italicum, rare and with a very restricted area, found in thirteen locations up to over 1800 m of altitude; C. cerdo for the Calabrian side of the National Park of Pollino; the first data for the presence of R. alpina at 1900 m altitude, the highest recorded in Italy and the discovery of larval stages on Italian alder (Alnus cordata), never ascertained in Italy. The Pollino National Park is confirmed as one of the areas of greatest national importance for the conservation of these xylophagous species linked to old forests

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding. In aggregate, these results might help to define novel approaches to COVID-19 based on SARS-CoV-2 entry inhibitors

Notulae to the Italian native vascular flora: 11.

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions. A new combination in the genus Pilosella is proposed. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1

Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988–June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994–1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted

Activation of GPBAR1 by BAR501, a selective synthetic agonist, reduces vascular inflammation and atherosclerosis in a mouse model of NAFLD-related cardiovascular disease

The purpose of this study was to evaluate the effect of GPBAR1 activation in a mouse model of atherosclerosis. For this study, Apolipoprotein E deficient mice (ApoE−/−), a standard model of atherosclerosis, were fed with HFD-F alone or in combination with BAR501 for 14 weeks and then sacrificed. The transcriptome analysis of the aorta showed an anti-inflammatory activity of BAR501 that downregulated the expression of many genes belonging to inflammatory pathways

Repositioning mifepristone as leukaemia inhibitory factor receptor antagonist for the treatment of pancreatic adenocarcinoma

Pancreatic cancer is leading cause of cancer mortality and is projected to become the second cause of cancer mortality in the next decade. While gene wide association studies and next generation sequencing analyses have identified molecular patterns and transcriptome profiles with prognostic relevance, therapeutic opportunities remain limited. Among the genes that were upregulated in pancreatic ductal adenocarcinomas (PDAC) the leukaemia inhibitory factor (LIF) has emerged as potential therapeutic candidate. Since there are no LIFR antagonists available for clinical use, we have developed an in-silico strategy to identify potential LIFR antagonists and drug reposition as LIFR antagonists. The results of these studies allowed the identification of mifepristone, a progesterone/glucocorticoid antagonist, clinical used in medical abortion, as potent LIFR antagonist

Combinatorial therapy with BAR502 and UDCA resets FXR and GPBAR1 signaling and reverses liver histopathology in a dietetic model of non-alcoholic fatty liver disease

Non-alcoholic steatosis (NAFLD) and steatohepatitis (NASH) are two highly prevalent human disorders for which therapy remains suboptimal. In the present study we have compared the effects of BAR502, a dual FXR/GPBAR1 ligand) alone or in combination with ursodeoxycholic acid (UDCA) in a model of NAFLD/NASH induced by feeding mice with a Western diet for 10 weeks

Analysis of oral and gut microbiota in children with dental cavities by Ion torrent 16s rRNA sequencing

The aim of our study is to evaluate the oral microbiome in distinct areas of the mouth of children with dental cavities (specifically the planktonic phase in saliva, the biofilm on the tooth and over the gingival epithelium) and understand whether or not the oral microbiome can be modulated through the use of probiotic Streptococcus Salivarius M18. The oral microbiome is also compared to the intestinal microbiome in order to understand if it exist a link between the two microbial communities and whether the changes in one of the two communities could affect the other

Insight in the treatment for pancreatic adenocarcinoma: discovery of the semisynthetic bile alcohol steroidal agonist BAR502 as a potent leukemia inhibitory factor receptor antagonist

The leukemia inhibitory factor (LIF), is a cytokine belonging to IL-6 family, whose overexpression correlate with poor prognosis in on cancer patients. LIF signaling is mediate by its binding to the heterodimeric LIF receptor (LIFR) complex formed by the LIFR receptor and Gp13o, leading to JAK1/STAT3 activation. The JAK/STAT3 pathway is over-regulated in several type of tumors, including pancreatic ductal adenocarcinoma (PDAC). Bile acids are steroid molecules that modulates the expression/activity of membrane and nuclear receptors, including the Farnesoid-X-Receptor (FXR) and G Protein Bile Acid Activated Receptor (GPBAR)1). In this study we have investigated whether ligands to FXR and GPBAR1 modulate LIF/LIFR pathway in ductal pancreatic acinar cells (PDAC) and whether these receptors are expressed in neoplastic tissues from a cohort PDCA patients.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV