Homeobox genes in normal and abnormal vasculogenesis

Homeobox containing genes are a family of transcription factors regulating normal development and controlling primary cellular processes (cell identity, cell division and differentiation) recently enriched by the discovery of their interaction with miRNAs and ncRNAs. Class I human homeobox genes (HOX genes) are characterized by a unique genomic network organization: four compact chromosomal loci where 39 sequence corresponding genes can be aligned with each other in 13 antero-posterior paralogous groups. The cardiovascular system is the first mesoderm organ-system to be generated during embryonic development; subsequently it generates the blood and lymphatic vascular systems. Cardiovascular remodelling is involved through homeobox gene regulation and deregulation in adult physiology (menstrual cycle and wound healing) and pathology (atherosclerosis, arterial restenosis, tumour angiogenesis and lymphangiogenesis). Understanding the role played by homeobox genes in endothelial and smooth muscle cell phenotype determination will be crucial in identifying the molecular processes involved in vascular cell differentiation, as well as to support future therapeutic strategies. We report here on the current knowledge of the role played by homeobox genes in normal and abnormal vasculogenesis and postulate a common molecular mechanism accounting for the involvement of homeobox genes in the regulation of the nuclear export of specific transcripts potentially capable of generating endothelial phenotype modification involved in new vessel formation

Prosystemin overexpression induces transcriptional modifications of defense-related and receptor-like kinase genes and reduces the susceptibility to Cucumber mosaic virus and its satellite RNAs in transgenic tomato plants

Open Access JournalSystemin is a plant signal peptide hormone involved in the responses to wounding and insect damage in the Solanaceae family. It works in the same signaling pathway of jasmonic acid (JA) and enhances the expression of proteinase inhibitors. With the aim of studying a role for systemin in plant antiviral responses, a tomato (Solanum lycopersicum) transgenic line overexpressing the prosystemin cDNA, i.e. the systemin precursor, was inoculated with Cucumber mosaic virus (CMV) strain Fny supporting either a necrogenic or a non-necrogenic satellite RNA (satRNA) variant. Transgenic plants showed reduced susceptibility to both CMV/satRNA combinations. While symptoms of the non-necrogenic inoculum were completely suppressed, a delayed onset of lethal disease occurred in about half of plants challenged with the necrogenic inoculum. RT-qPCR analysis showed a correlation between the systemin-mediated reduced susceptibility and the JA biosynthetic and signaling pathways (e.g. transcriptional alteration of lipoxygenase D and proteinase inhibitor II). Moreover, transgenically overexpressed systemin modulated the expression of a selected set of receptor-like protein kinase (RLK) genes, including some playing a known role in plant innate immunity. A significant correlation was found between the expression profiles of some RLKs and the systemin-mediated reduced susceptibility to CMV/satRNA. These results show that systemin can increase plant defenses against CMV/satRNA through transcriptional reprogramming of diverse signaling pathways

The Hemodynamics of Aneurysms Treated with Flow-Diverting Stents Considering both Stent and Aneurysm/Artery Geometries

Flow diverting stents are deployed to reduce the blood flow into the aneurysm, which would thereby induce thrombosis in the aneurysm sac; the stents prevent its rupture. The present study aimed to examine and quantify the impacts of different flow stents on idealized configurations of the cerebral artery. In our study, we considered a spherical sidewall aneurysm located on curved and tortuous idealized artery vessels and three stents with different porosities (70, 80 and 90%) for deployment. Using computational fluid dynamics, the local hemodynamics in the presence and absence of the stents were simulated, respectively, under the assumption that the blood flow was unsteady and non-Newtonian. The hemodynamic parameters, such as the intra-aneurysmal flow, velocity field and wall shear stress and its related indices, were examined and compared among the 12 cases simulated. The results illustrated that with the stent deployment, the intra-aneurysmal flow and the wall shear stress and its related indices were considerably modified depending on both stent and aneurysm/artery geometries, and that the intra-aneurysmal relative residence time increased rapidly with decreasing stent porosity in all the vessel configurations. These results also inform the rationale for selecting stents for treating aneurysms of different configurations

HOX D13 expression across 79 tumor tissue types.

HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas-tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis

Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant : An Italian Multicenter Experience

Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9\u2013306) since LT and PMR was performed after 2.4 months (0\u201343.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50\u2013365); median post-operative overall stay 5 days (2\u201311). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7\u2013213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12\u201374), respectively, with a median OS of 51 months (95%CI 24\u201378). Conclusion: Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival

The SURF (Italian observational study for renal insufficiency evaluation in liver transplant recipients): A post-hoc between-sex analysis

Background: Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage. Methods: All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2 at inclusion and follow-up visit. Results: Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR < 60 mL/min/1.73 m2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O'Riordan eGFR levels were observed at time of transplant and study initial visit (p = 0.0005 and 0.0299 respectively), but not at follow-up. Conclusions: Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth

Correction to: Diffusion, outcomes and implementation of minimally invasive liver surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Luca Aldrighetti, Francesca Ratti, Umberto Cillo, Alessandro Ferrero, Giuseppe Maria Ettorre, Alfredo Guglielmi, Felice Giuliante, Fulvio Calise on behalf of the Italian Group of Minimally Invasive Liver Surgery (I GO MILS) The collaborators are: Raffaele Dalla Valle, AOU Parma, Parma; Vincenzo Mazzaferro, Istituto Nazionale Tumori, Milano; Elio Jovine, Ospedale Maggiore, Bologna; Luciano Gregorio De Carlis, Ospedale Niguarda Ca\u2019 Granda, Milano; Ugo Boggi, AOU Pisana, Pisa; Salvatore Gruttadauria, ISMETT, Palermo; Fabrizio Di Benedetto, AOU Policlinico di Modena, Modena; Paolo Reggiani, Ospedale Maggiore Policlinico, Milano; Stefano Berti, Ospedale Civile S.Andrea, La Spezia; Graziano Ceccarelli, Ospedale San Donato, Arezzo; Leonardo Vincenti, AOU Consorziale Policlinico, Bari; Giulio Belli, Ospedale SM Loreto Nuovo, Napoli; Guido Torzilli, Istituto Clinico Humanitas, Rozzano; Fausto Zamboni, Ospedale Brotzu, Cagliari; Andrea Coratti, AOU Careggi, Firenze; Pietro Mezzatesta, Casa di Cura La Maddalena, Palermo; Roberto Santambrogio, AO San Paolo, Milano; Giuseppe Navarra, AOU Policlinico G. Martino, Messina; Antonio Giuliani, AO R.N. Cardarelli, Napoli; Antonio Daniele Pinna, Policlinico Sant\u2019Orsola Malpighi, Bologna; Amilcare Parisi, AO Santa Maria di Terni, Terni; Michele Colledan, AO Papa Giovanni XXIII, Bergamo; Abdallah Slim, AO Desio e Vimercate, Vimercate; Adelmo Antonucci, Policlinico di Monza, Monza; Gian Luca Grazi, Istituto Nazionale Tumori Regina Elena, Roma; Antonio Frena, Ospedale Centrale, Bolzano; Giovanni Sgroi, AO Treviglio-Caravaggio, Treviglio; Alberto Brolese, Ospedale S.Chiara, Trento; Luca Morelli, AOU Pisana, Pisa; Antonio Floridi, AO Ospedale Maggiore, Crema; Alberto Patriti, Ospedale San Matteo degli Infermi, Spoleto; Luigi Veneroni, Ospedale Infermi AUSL Romagna, Rimini; Giorgio Ercolani, Ospedale Morgagni Pierantoni, Forl\uec; Luigi Boni, AOU Fondazione Macchi, Varese; Pietro Maida, Ospedale Villa Betania, Napoli; Guido Griseri, Ospedale San Paolo, Savona; Andrea Percivale, Ospedale Santa Corona, Pietraligure; Marco Filauro, AO Galliera, Genova; Silvio Guerriero, Ospedale San Martino, Belluno; Giuseppe Tisone, Policlinico Tor Vergata, Roma; Raffaele Romito, AOU Maggiore della Carit\ue0, Novara; Umberto Tedeschi, AOU Integrata Verona, Verona; Giuseppe Zimmitti, Fondazione Poliambulanza, Brescia

Liver transplantation as last-resort treatment for patients with bile duct injuries following cholecystectomy: A multicenter analysis

Background Liver transplantation (LT) has been used as a last resort in patients with end-stage liver disease due to bile duct injuries (BDI) following cholecystectomy. Our study aimed to identify and evaluate factors that cause or contribute to an extended liver disease that requires LT as ultimate solution, after BDI during cholecystectomy. Methods Data from 8 high-volume LT centers relating to patients who underwent LT after suffering BDI during cholecystectomy were prospectively collected and retrospectively analyzed. Results Thirty-four patients (16 men, 18 women) with a median age of 45 (range 22-69) years were included in this study. Thirty of them (88.2%) underwent LT because of liver failure, most commonly as a result of secondary biliary cirrhosis. The median time interval between BDI and LT was 63 (range 0-336) months. There were 23 cases (67.6%) of postoperative morbidity, 6 cases (17.6%) of post-transplant 30-day mortality, and 10 deaths (29.4%) in total after LT. There was a higher probability that patients with concomitant vascular injury (hazard ratio 10.69, P=0.039) would be referred sooner for LT. Overall survival following LT at 1, 3, 5 and 10 years was 82.4%, 76.5%, 73.5% and 70.6%, respectively. Conclusion LT for selected patients with otherwise unmanageable BDI following cholecystectomy yields acceptable long-term outcomes

Evolution of minimally invasive techniques and surgical outcomes of ALPPS in Italy: a comprehensive trend analysis over 10 years from a national prospective registry

BackgroundSince 2012, Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has encountered several modifications of its original technique. The primary endpoint of this study was to analyze the trend of ALPPS in Italy over a 10-year period. The secondary endpoint was to evaluate factors affecting the risk of morbidity/mortality/post-hepatectomy liver failure (PHLF).MethodsData of patients submitted to ALPPS between 2012 and 2021 were identified from the ALPPS Italian Registry and evaluation of time trends was performed.ResultsFrom 2012 to 2021, a total of 268 ALPPS were performed within 17 centers. The number of ALPPS divided by the total number of liver resections performed by each center slightly declined (APC = - 2.0%, p = 0.111). Minimally invasive (MI) approach significantly increased over the years (APC = + 49.5%, p = 0.002). According to multivariable analysis, MI completion of stage 1 was protective against 90-day mortality (OR = 0.05, p = 0.040) as well as enrollment within high-volume centers for liver surgery (OR = 0.32, p = 0.009). Use of interstage hepatobiliary scintigraphy (HBS) and biliary tumors were independent predictors of PHLF.ConclusionsThis national study showed that use of ALPPS only slightly declined over the years with an increased use of MI techniques, leading to lower 90-day mortality. PHLF still remains an open issue