| 1. |
- Abrate, Alberto, et al.
(author)
-
Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression
- 2014
-
In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 50:14, s. 2478-2488
-
Journal article (peer-reviewed)abstract
- Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase:: uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease.
|
|
| 2. |
- Esposito, Marco, 1965, et al.
(author)
-
Short implants versus longer implants in vertically augmented atrophic mandibles: A systematic review of randomised controlled trials with a 5-year post-loading follow-up.
- 2019
-
In: International journal of oral implantology (New Malden, London, England). - 2631-6439. ; 12:3, s. 267-280
-
Journal article (peer-reviewed)abstract
- To compare the clinical outcome of fixed prostheses supported by 4- to 8-mm-long implants with prostheses supported by longer implants placed in vertically augmented atrophic mandibles after a follow-up of 5 years in function.The Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE were searched up to 1st September 2018 for randomised controlled trials (RCTs) with a follow-up of at least 5 years in function comparing fixed prostheses supported by 4- to 8-mm-long implants with prostheses supported by longer implants placed in vertically augmented atrophic mandibles. Outcome measures were prosthesis failure, implant failures, augmentation procedure failures, complications, and peri-implant marginal bone level changes. Screening of eligible studies, assessment of the risk of bias and data extraction were conducted in duplicate and independently by two review authors. The statistical unit of the analysis was the prosthesis. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CIs).Four eligible RCTs that included originally 135 patients were included. Two RCTs had a parallel-group design and two a split-mouth design. Short implants were 5.0 to 6.6 mm long and were compared with longer implants placed in posterior mandibles augmented with interpositional blocks of bone substitutes. All trials were judged at unclear risk of bias. Twelve (14%) bone augmentation procedures failed to achieve the planned bone height to allow placement of implants with the planned length. Five years after loading, 28 patients (21%) had dropped out from the four RCTs. There were no differences for patients having prosthesis (RR = 1.46; 95% CI: 0.52 to 4.09; P = 0.47; I2 = 0%) or implant (RR = 1.00; 95% CI: 0.31 to 3.21; P = 1.00; I2 = 0%) failures between the two interventions, but there were more patients experiencing complications (RR = 4.72; 95% CI: 2.43 to 9.17; P < 0.00001; I2 = 0%) and peri-implant marginal bone loss (mean difference = 0.60 mm; 95% CI: 0.36 to 0.83; P < 0.00001; I2 = 45%) at longer implants in augmented bone.Five years after loading, prosthetic and implant failures were similar between the two interventions, but complications and peri-implant marginal bone loss were higher and more severe at longer implants placed in vertically augmented mandibles. Larger trials and longer follow-ups up to 10 years after loading are needed to confirm or reject the present preliminary findings. However in the meantime short implants could be the preferable option.
|
|
| 3. |
- Hallan, Supandeep Singh, et al.
(author)
-
Design of Nanosystems for the Delivery of Quorum Sensing Inhibitors : A Preliminary Study
- 2020
-
In: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:23
-
Journal article (peer-reviewed)abstract
- Biofilm production is regulated by the Quorum Sensing system. Nowadays, Quorum Sensing represents an appealing target to design new compounds to increase antibiotics effects and avoid development of antibiotics multiresistance. In this research the use of liposomes to target two novel synthetic biofilm inhibitors is presented, focusing on a preformulation study to select a liposome composition for in vitro test. Five different liposome (LP) formulations, composed of phosphatidyl choline, cholesterol and charged surfactant (2:1:1, molar ratio) have been prepared by direct hydration and extrusion. As charged surfactants dicetyl phosphate didecyldimethylammonium chloride, di isobutyl phenoxy ethyl dimethyl benzyl ammonium chloride and stearylamine (SA) and have been used. Liposome charge, size and morphology were investigated by zeta potential, photon correlation spectroscopy, small angle x-ray spectroscopy and electron microscopy. LP-SA was selected for the loading of biofilm inhibitors and subjected to high performance liquid chromatography for entrapment capacity evaluation. LP-SA loaded inhibitors showed a higher diameter (223.6 nm) as compared to unloaded ones (205.7 nm) and a dose-dependent anti-biofilm effect mainly after 48 h of treatment, while free biofilm inhibitors loose activity. In conclusion, our data supported the use of liposomes as a strategy to enhance biofilm inhibitors effect.
|
|
| 4. |
- Henein, Michael Y., et al.
(author)
-
Biomarkers predict in-hospital major adverse cardiac events in covid-19 patients : A multicenter international study
- 2021
-
In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:24
-
Journal article (peer-reviewed)abstract
- Background: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19.Methods: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE).Results: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan–Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001).Conclusions: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.
|
|
| 5. |
- Nagueh, Sherif F., et al.
(author)
-
Interobserver Variability in Applying American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 Guidelines for Estimation of Left Ventricular Filling Pressure
- 2019
-
In: Circulation Cardiovascular Imaging. - 1941-9651 .- 1942-0080. ; 12:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND:Assessment of left ventricular (LV) filling pressure is among the important components of a comprehensive echocardiographic report. Previous studies noted wide limits of agreement using 2009 American Society of Echocardiography/European Association of Echocardiography guidelines, but reproducibility of 2016 guidelines update in estimating LV filling pressure is unknown.METHODS:Echocardiographic and hemodynamic data were obtained from 50 patients undergoing cardiac catheterization for clinical indications. Clinical and echocardiographic findings but not invasive hemodynamics were provided to 4 groups of observers, including experienced echocardiographers and cardiology fellows. Invasively acquired LV filling pressure was the gold standard.RESULTS:In group I of 8 experienced echocardiographers from the guidelines writing committee, sensitivity for elevated LV filling pressure was 92% for all observers, and specificity was 93 +/- 6%. Fleiss kappa-value for the agreement in group I was 0.80. In group II of 4 fellows in training, sensitivity was 91 +/- 2%, and specificity was 95 +/- 2%. Fleiss kappa-value for the agreement in group II was 0.94. In group III of 9 experienced echocardiographers who had not participated in drafting the guidelines, sensitivity was 88 +/- 5%, and specificity was 91 +/- 7%. Fleiss kappa-value for the agreement in group III was 0.76. In group IV of 7 other fellows, sensitivity was 91 +/- 3%, and specificity was 92 +/- 5%. Fleiss kappa-value for the agreement in group IV was 0.89.CONCLUSIONS:There is a good level of agreement and accuracy in the estimation of LV filling pressure using the American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 recommendations update, irrespective of the experience level of the observer.
|
|
| 6. |
- Poongavanam, Vasanthanathan, et al.
(author)
-
Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors : binding mode insights through magnesium complexation and site-directed mutagenesis studies
- 2018
-
In: MedChemComm. - : ROYAL SOC CHEMISTRY. - 2040-2503 .- 2040-2511. ; 9:3, s. 562-575
-
Journal article (peer-reviewed)abstract
- Persistent HIV infection requires lifelong treatment and among the 2.1 million new HIV infections that occur every year there is an increased rate of transmitted drug-resistant mutations. This fact requires a constant and timely effort in order to identify and develop new HIV inhibitors with innovative mechanisms. The HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only viral encoded enzyme that still lacks an efficient inhibitor despite the fact that it is a well-validated target whose functional abrogation compromises viral infectivity. Identification of new drugs is a long and expensive process that can be speeded up by in silico methods. In the present study, a structure-guided screening is coupled with a similarity-based search on the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of the 45 compounds selected for experimental testing, 15 inhibited the RNase H function below 100 mu M with three hits exhibiting IC50 values < 10 mu M. The most active compound, AA, inhibits HIV-1 RNase H with an IC50 of 5.1 mu M and exhibits a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide valuable insight into the binding mode of newly identified compounds; for instance, compound AA involves extensive interactions with a lipophilic pocket formed by Ala502, Lys503, and Trp (406, 426 and 535) and polar interactions with Arg557 and the highly conserved RNase H primer-grip residue Asn474. The structural insights obtained from this work provide the bases for further lead optimization.
|
|
