Neurotrophic Activity and Its Modulation by Zinc Ion of a Dimeric Peptide Mimicking the Brain-Derived Neurotrophic Factor N-Terminal Region

Brain-derived neurotrophic factor (BDNF) is a neurotrophin (NT) essential for neuronal development and synaptic plasticity. Dysregulation of BDNF signaling is implicated in different neurological disorders. The direct NT administration as therapeutics has revealed to be challenging. This has prompted the design of peptides mimicking different regions of the BDNF structure. Although loops 2 and 4 have been thoroughly investigated, less is known regarding the BDNF N-terminal region, which is involved in the selective recognition of the TrkB receptor. Herein, a dimeric form of the linear peptide encompassing the 1-12 residues of the BDNF N-terminal (d-bdnf) was synthesized. It demonstrated to act as an agonist promoting specific phosphorylation of TrkB and downstream ERK and AKT effectors. The ability to promote TrkB dimerization was investigated by advanced fluorescence microscopy and molecular dynamics (MD) simulations, finding activation modes shared with BDNF. Furthermore, d-bdnf was able to sustain neurite outgrowth and increase the expression of differentiation (NEFM, LAMC1) and polarization markers (MAP2, MAPT) demonstrating its neurotrophic activity. As TrkB activity is affected by zinc ions in the synaptic cleft, we first verified the ability of d-bdnf to coordinate zinc and then the effect of such complexation on its activity. The d-bdnf neurotrophic activity was reduced by zinc complexation, demonstrating the role of the latter in tuning the activity of the new peptido-mimetic. Taken together our data uncover the neurotrophic properties of a novel BDNF mimetic peptide and pave the way for future studies to understand the pharmacological basis of d-bdnf action and develop novel BDNF-based therapeutic strategies

Guidelines on the management of abdominal aortic aneurysms: updates from the Italian Society of Vascular and Endovascular Surgery (SICVE)

The objective of these Guidelines was to revise and update the previous 2016 Italian Guidelines on Abdominal Aortic Aneurysm Disease, in accordance with the National Guidelines System (SNLG), to guide every practitioner toward the most correct management pathway for this pathology. The methodology applied in this update was the GRADE-SIGN version methodology, following the instructions of the AGREE quality of reporting checklist as well. The first methodological step was the formulation of clinical questions structured according to the PICO (Population, Intervention, Comparison, Outcome) model according to which the Recommendations were issued. Then, systematic reviews of the Literature were carried out for each PICO question or for homogeneous groups of questions, followed by the selection of the articles and the assessment of the methodological quality for each of them using qualitative checklists. Finally, a Considered Judgment form was filled in for each clinical question, in which the features of the evidence as a whole are assessed to establish the transition from the level of evidence to the direction and strength of the recommendations. These guidelines outline the correct management of patients with abdominal aortic aneurysm in terms of screening and surveillance. Medical management and indication for surgery are discussed, as well as preoperative assessment regarding patients' background and surgical risk evaluation. Once the indication for surgery has been established, the options for traditional open and endovascular surgery are described and compared, focusing specifically on patients with ruptured abdominal aortic aneurysms as well. Finally, indications for early and late postoperative follow-up are explained. The most recent evidence in the Literature has been able to confirm and possibly modify the previous recommendations updating them, likewise to propose new recommendations on prospectively relevant topics

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM)

: The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended

Position Paper on Young Vascular Surgeons Training of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS):State of the Art and Perspectives

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty

IL-1 family cytokines and receptors in IgG4-related disease

BACKGROUND/AIM: The IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect almost any organ, often associated with eosinophilia and increased levels of IgE and IgG4. Overexpression in tissues of Th2-related cytokines but also of IFN-γ has been reported. Given the major role of Il-1 family cytokines in inducing and regulating inflammation, and the paucity of data so far available in IgG-RD, we performed a comprehensive analysis of IL-18, related IL-1 family cytokines and soluble receptors in these patients. PATIENTS AND METHODS: Fifteen patients fulfilling the criteria for the diagnosis of IgG4-RD and 80 blood donors as control were recruited. Cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein -IL-18BP-) were measured in sera by multiarray ELISA assay. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. RESULTS: Half of the patients had a multiorgan disease, mainly affecting retroperitoneum, lymph nodes and pancreas. sIL-1R1 (p=0.0001), sIL-1R2 (p=0.0024), ST2/sIL-1R4 (p=0.002) were significantly increased in IgG4-RD sera compared with healthy controls; sIL-R3 was significantly lower in patients vs controls (p=0,0006). CONCLUSIONS: The increased levels of the soluble forms of the two IL-1 receptors IL-1R1 and IL-1R2 suggest the need to dampen IL-1-mediated inflammation at the tissue level. Elevated circulating ST2/sIL-1R4 levels may represent the marker of an ongoing protective mechanism, but their contribution to organ damage cannot be excluded. On the whole, the data suggest a tight control of IL-1 family cytokines signalling in IgG4-RD

Visceral and renal artery aneurysms

none6noneGiovanni Pratesi, Gian Antonio Boschetti, Luigi F. Rinaldi, Martina Bastianon, Sara Di Gregorio, Domenico PalomboPratesi, Giovanni; Antonio Boschetti, Gian; Rinaldi, Luigi F.; Bastianon, Martina; Di Gregorio, Sara; Palombo, Domenic