Publications by authors named "Marco De Spirito"

121 Publications

Visco-Hyperelastic Characterization of the Equine Immature Zona Pellucida.

Materials (Basel) 2021 Mar 5;14(5). Epub 2021 Mar 5.

Dipartimento di Meccanica, Matematica e Management, Politecnico di Bari, 70125 Bari, Italy.

This article presents a very detailed study on the mechanical characterization of a highly nonlinear material, the immature equine zona pellucida (ZP) membrane. The ZP is modeled as a visco-hyperelastic soft matter. The Arruda-Boyce constitutive equation and the two-term Prony series are identified as the most suitable models for describing the hyperelastic and viscous components, respectively, of the ZP's mechanical response. Material properties are identified via inverse analysis based on nonlinear optimization which fits nanoindentation curves recorded at different rates. The suitability of the proposed approach is fully demonstrated by the very good agreement between AFM data and numerically reconstructed force-indentation curves. A critical comparison of mechanical behavior of two immature ZP membranes (i.e., equine and porcine ZPs) is also carried out considering the information on the structure of these materials available from electron microscopy investigations documented in the literature.
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http://dx.doi.org/10.3390/ma14051223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961360PMC
March 2021

Investigation of the Membrane Fluidity Regulation of Fatty Acid Intracellular Distribution by Fluorescence Lifetime Imaging of Novel Polarity Sensitive Fluorescent Derivatives.

Int J Mol Sci 2021 Mar 18;22(6). Epub 2021 Mar 18.

Neuroscience Department, Biophysics Section, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Free fatty acids are essential structural components of the cell, and their intracellular distribution and effects on membrane organelles have crucial roles in regulating the metabolism, development, and cell cycle of most cell types. Here we engineered novel fluorescent, polarity-sensitive fatty acid derivatives, with the fatty acid aliphatic chain of increasing length (from 12 to 18 carbons). As in the laurdan probe, the lipophilic acyl tail is connected to the environmentally sensitive dimethylaminonaphthalene moiety. The fluorescence lifetime imaging analysis allowed us to monitor the intracellular distribution of the free fatty acids within the cell, and to simultaneously examine how the fluidity and the microviscosity of the membrane environment influence their localization. Each of these probes can thus be used to investigate the membrane fluidity regulation of the correspondent fatty acid intracellular distribution. We observed that, in PC-12 cells, fluorescent sensitive fatty acid derivatives with increased chain length compartmentalize more preferentially in the fluid regions, characterized by a low microviscosity. Moreover, fatty acid derivatives with the longest chain compartmentalize in lipid droplets and lysosomes with characteristic lifetimes, thus making these probes a promising tool for monitoring lipophagy and related events.
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http://dx.doi.org/10.3390/ijms22063106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002861PMC
March 2021

Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) detection as a rapid and convenient screening test for cystinuria.

Clin Chim Acta 2021 Mar 29;518:128-133. Epub 2021 Mar 29.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. Electronic address:

Background: Cystinuria is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. The Brand's test, used for diagnosis, requires dangerous substances, so has been replaced with high-performance liquid chromatography with fluorimetric detection (HPLC-FL). However, this technique requires the use of complex equipment. Infrared spectroscopy, universally used for stone analysis, recently was employed to detect insoluble cystine in urine. The aim of this study is to evaluate Infrared Spectroscopy combined with chemometric analysis as screening method to identify those patients requiring confirmation by HPLC-FL analysis.

Methods: We examined 24 h urine specimens from 57 patients. The quantitative analysis was performed by HPLC-FL. The infrared spectroscopic urine sediment analysis was performed with an ATR accessory (ATR-FTIR). Urine is centrifuged, the supernatant is discarded, and the sediment is dried on to the ATR prism surface. Statistical analysis was performed using a custom-made software developed in MATLAB environment.

Results: The HPLC-FL determination showed a normal excretion of cystine in 49 samples and an abnormal excretion in the remaining 8 samples. The ATR-FTIR analysis combined with a statistical approach gives a sensitivity of 1.0 and a specificity of 0.82 were obtained.

Conclusions: The introduction of the ATR-FTIR technique in our clinical laboratory setting may reduce time and cost analysis for diagnosis of cystinuria.
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http://dx.doi.org/10.1016/j.cca.2021.03.017DOI Listing
March 2021

Face masks and nanotechnology: Keep the blue side up.

Nano Today 2021 Apr 13;37:101077. Epub 2021 Jan 13.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.

Coronavirus Disease 2019 (COVID-19) is one of the biggest challenges of the 21st century. While researchers are working on vaccine development and elucidating the mechanism of action and evolution of the harmful SARS-CoV-2, the current most important public health measure, second only to social distancing, is the obligatory wearing of facial protection. The Centers for Disease Control and Prevention recommended in April 2020 that the public wear face coverings in areas with high rates of transmission based on epidemiological evidence on the strong relationship between mask wearing and pandemic control. This protection against SARS-CoV-2 and other airborne pathogens, boost the design and production of innovative solutions by industry stakeholders. Nanoparticles, nanofibers, and other pioneering technologies based on nanomaterials have been introduced in mask production chains to improve performance and confer antiviral properties. During an emergency like COVID-19, these products directly available to the public should be carefully analyzed in terms of efficacy and possible long-term effects on the wearers' skin and lungs as well as on the environment. This opinion paper provides a wealth of information on the role of nanotechnologies in improving the performance of facial masks and on possible future consequences caused by a poorly regulated use of nanotechnology in textiles.
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http://dx.doi.org/10.1016/j.nantod.2021.101077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833187PMC
April 2021

Label-free metabolic clustering through unsupervised pixel classification of multiparametric fluorescent images.

Anal Chim Acta 2021 Mar 31;1148:238173. Epub 2020 Dec 31.

Fondazione Policlinico Gemelli IRCSS, Rome, Italy; Department of Neuroscience, Section of Biophysics, Università Cattolica Del Sacro Cuore, Rome, Italy. Electronic address:

Autofluorescence microscopy is a promising label-free approach to characterize NADH and FAD metabolites in live cells, with potential applications in clinical practice. Although spectrally resolved lifetime imaging techniques can acquire multiparametric information about the biophysical and biochemical state of the metabolites, these data are evaluated at the whole-cell level, thus providing only limited insights in the activation of metabolic networks at the microscale. To overcome this issue, here we introduce an artificial intelligence-based analysis that, leveraging the multiparametric content of spectrally resolved lifetime images, allows to detect and classify, through an unsupervised learning approach, metabolic clusters, which are regions having almost uniform metabolic properties. This method contextually detects the cellular mitochondrial turnover and the metabolic activation state of intracellular compartments at the pixel level, described by two functions: the cytosolic activation state (CAF) and the mitochondrial activation state (MAF). This method was applied to investigate metabolic changes elicited in the breast cancer cell line MCF-7 by specific inhibitors of glycolysis and electron transport chain, and by the deregulation of a specific mitochondrial enzyme (ACO2) leading to defective aerobic metabolism associated with tumor growth. In this model, mitochondrial fraction undergoes to a 13% increase upon ACO2 overexpression and the MAF function changes abruptly by altering the metabolic state of about the 25% of the mitochondrial pixels.
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http://dx.doi.org/10.1016/j.aca.2020.12.048DOI Listing
March 2021

Evaluation of a generalized knowledge-based planning performance for VMAT irradiation of breast and locoregional lymph nodes-Internal mammary and/or supraclavicular regions.

PLoS One 2021 15;16(1):e0245305. Epub 2021 Jan 15.

Università Cattolica del Sacro Cuore, Rome, Italy.

Purpose: To evaluate the performance of eleven Knowledge-Based (KB) models for planning optimization (RapidPlantm (RP), Varian) of Volumetric Modulated Arc Therapy (VMAT) applied to whole breast comprehensive of nodal stations, internal mammary and/or supraclavicular regions.

Methods And Materials: Six RP models have been generated and trained based on 120 VMAT plans data set with different criteria. Two extra-structures were delineated: a PTV for the optimization and a ring structure. Five more models, twins of the previous models, have been created without the need of these structures.

Results: All models were successfully validated on an independent cohort of 40 patients, 30 from the same institute that provided the training patients and 10 from an additional institute, with the resulting plans being of equal or better quality compared with the clinical plans. The internal validation shows that the models reduce the heart maximum dose of about 2 Gy, the mean dose of about 1 Gy and the V20Gy of 1.5 Gy on average. Model R and L together with model B without optimization structures ensured the best outcomes in the 20% of the values compared to other models. The external validation observed an average improvement of at least 16% for the V5Gy of lungs in RP plans. The mean heart dose and for the V20Gy for lung IPSI were almost halved. The models reduce the maximum dose for the spinal canal of more than 2 Gy on average.

Conclusions: All KB models allow a homogeneous plan quality and some dosimetric gains, as we saw in both internal and external validation. Sub-KB models, developed by splitting right and left breast cases or including only whole breast with locoregional lymph nodes, have shown good performances, comparable but slightly worse than the general model. Finally, models generated without the optimization structures, performed better than the original ones.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245305PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810311PMC
January 2021

Nuclear Localization of PTTG1 Promotes Migration and Invasion of Seminoma Tumor through Activation of MMP-2.

Cancers (Basel) 2021 Jan 8;13(2). Epub 2021 Jan 8.

International Scientific Institute "Paul VI", ISI, Fondazione Policlinico 'A. Gemelli' IRCCS, 00100 Rome, Italy.

(1) Background: PTTG1 sustains the invasiveness of several cancer types. We previously reported that in seminomas, PTTG1 was detected in the peripheral area of the tumor and in the leading infiltrative edge. Here, we investigate the PTTG1 role on the invasive properties of seminoma. (2) Methods: three seminoma cell lines were used as in vitro model. PTTG1 levels and localization were investigated by biochemical and immunofluorescence analyses. Wound-healing, Matrigel invasion assays, and zymography were applied to study migratory and invasive capability of the cell lines. RNA interference and overexpression experiments were performed to address the PTTG1 role in seminoma invasiveness. PTTG1 and its target MMP-2 were analyzed in human testicular tumors using the Atlas database. (3) Results: PTTG1 was highly and differentially expressed in the seminoma cell lines. Nuclear PTTG1 was positively correlated to the aggressive phenotype. Its modulation confirms these results. Atlas database analysis revealed that PTTG1 was localized in the nucleus in seminoma compared with non-seminoma tumors, and that MMP-2 levels were significantly higher in seminomas. (4) Conclusions: nuclear PTTG1 promotes invasiveness of seminoma cell lines. Atlas database supported these results. These data lead to the hypothesis that nuclear PTTG1 is an eligible prognostic factor in seminomas.
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http://dx.doi.org/10.3390/cancers13020212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826632PMC
January 2021

Fourier Transform Infrared Spectroscopy as a useful tool for the automated classification of cancer cell-derived exosomes obtained under different culture conditions.

Anal Chim Acta 2020 Dec 9;1140:219-227. Epub 2020 Oct 9.

Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica Del Sacro Cuore, Roma, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. Electronic address:

Exosomes possess great potential as cancer biomarkers in personalized medicine due to their easy accessibility and capability of representing their parental cells. To boost the translational process of exosomes in diagnostics, the development of novel and effective strategies for their label-free and automated characterization is highly desirable. In this context, Fourier Transform Infrared Spectroscopy (FTIR) has great potential as it provides direct access to specific biomolecular bands that give compositional information on exosomes in terms of their protein, lipid and genetic content. Here, we used FTIR spectroscopy in the mid-Infrared (mid-IR) range to study exosomes released from human colorectal adenocarcinoma HT-29 cancer cells cultured in different media. To this purpose, cells were studied in well-fed condition of growth, with 10% of exosome-depleted FBS (EVd-FBS), and under serum starvation with 0.5% EVd-FBS. Our data show the presence of statistically significant differences in the shape of the Amide I and II bands in the two conditions. Based on these differences, we showed the possibility to automatically classify cancer cell-derived exosomes using Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA); we tested the effectiveness of the classifier with a cross-validation approach, obtaining very high accuracy, precision, and recall. Aside from classification purposes, our FTIR data provide hints on the underlying cellular mechanisms responsible for the compositional differences in exosomes, suggesting a possible role of starvation-induced autophagy.
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http://dx.doi.org/10.1016/j.aca.2020.09.037DOI Listing
December 2020

Erythrocyte membrane fluidity as a marker of diabetic retinopathy in type 1 diabetes mellitus.

Eur J Clin Invest 2020 Nov 19:e13455. Epub 2020 Nov 19.

Fondazione Policlinico Universitario A, Gemelli IRCSS, Rome, Italy.

Background: A high level of glycosylated haemoglobin (HbA1c), which is a nonenzymatic glycosylation product, is correlated with an increased risk of developing microangiopathic complications in Diabetes Mellitus (DM). Erythrocyte membrane fluidity could provide a complementary index to monitor the development of complications since it is influenced by several hyperglycaemia-induced pathways and other independent risk factors.

Materials And Methods: 15 healthy controls and 33 patients with long-duration (≥20 years) type 1 Diabetes Mellitus (T1DM) were recruited. Diabetic subjects were classified into two groups: T1DM, constituted by 14 nonretinopathic patients, and T1DM + RD, constituted by 19 patients in any stage of diabetic retinopathy. Red blood cells (RBC) were incubated with the fluorescent Laurdan probe and median values of Generalized Polarization (GP), representative of membrane fluidity, were compared between the two groups. Baseline characteristics among groups have been compared with Student's t test or ANOVA. Values of P < .05 were considered statistically significant.

Results: All the participants were comparable for age, Body Mass Index (BMI), creatinine and lipid profile. The duration of diabetes was similar for T1DM (34.4 ± 7.8 years) and T1DM + RD (32.8 ± 7.5 years) subjects as well as values of HbA1c: (55.6 ± 8.1) mmol/mol for T1DM and (61.2 ± 11.0) mmol/mol for T1DM + RD, respectively. Erythrocyte plasmatic membranes of RD patients were found to be more fluid (GP: 0.40 ± 0.04) than non-RD patients (GP: 0.43 ± 0.03) with a statistically significant difference (P = .035).

Conclusions: Altered erythrocyte membrane fluidity may therefore represent a marker of retinopathy in T1DM patients as a result of post-translational modifications of multifactorial aetiology (nonenzymatic glycosylation of proteins, generation of reactive oxygen species, lipid peroxidation).
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http://dx.doi.org/10.1111/eci.13455DOI Listing
November 2020

Unsupervised clustering of multiparametric fluorescent images extends the spectrum of detectable cell membrane phases with sub-micrometric resolution.

Biomed Opt Express 2020 Oct 21;11(10):5728-5744. Epub 2020 Sep 21.

Fondazione Policlinico Gemelli IRCSS, 00168 Rome, Italy.

Solvatochromic probes undergo an emission shift when the hydration level of the membrane environment increases and are commonly used to distinguish between solid-ordered and liquid-disordered phases in artificial membrane bilayers. This emission shift is currently limited in unraveling the broad spectrum of membrane phases of natural cell membranes and their spatial organization. Spectrally resolved fluorescence lifetime imaging can provide pixel-resolved multiparametric information about the biophysical state of the membranes, like membrane hydration, microviscosity and the partition coefficient of the probe. Here, we introduce a clustering based analysis that, leveraging the multiparametric content of spectrally resolved lifetime images, allows us to classify through an unsupervised learning approach multiple membrane phases with sub-micrometric resolution. This method extends the spectrum of detectable membrane phases allowing to dissect and characterize up to six different phases, and to study real-time phase transitions in cultured cells and tissues undergoing different treatments. We applied this method to investigate membrane remodeling induced by high glucose on PC-12 neuronal cells, associated with the development of diabetic neuropathy. Due to its wide applicability, this method provides a new paradigm in the analysis of environmentally sensitive fluorescent probes.
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http://dx.doi.org/10.1364/BOE.399655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587257PMC
October 2020

Red blood cells membrane micropolarity as a novel diagnostic indicator of type 1 and type 2 diabetes.

Anal Chim Acta X 2019 Nov 14;3:100030. Epub 2019 Oct 14.

Fondazione Policlinico Universitario A, Gemelli IRCSS, Rome, Italy.

Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p<0.01). The role of serum cholesterol pool in determining these differences was investigated, and other factors potentially altering the response of the probe were considered in view of developing a clinical assay based on RBC membrane micropolarity. These preliminary data pave the way for the development of an innovative assay which could become a tool for diagnosis and progression monitoring of type 1 and type 2 diabetes.
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http://dx.doi.org/10.1016/j.acax.2019.100030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587021PMC
November 2019

Searching for the Mechanical Fingerprint of Pre-diabetes in T1DM: A Case Report Study.

Front Bioeng Biotechnol 2020 29;8:569978. Epub 2020 Sep 29.

Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, Rome, Italy.

We report the case of a 38 year-old Caucasian man enrolled in a study aimed at investigating the physical properties of red blood cells (RBCs) using advanced microscopy techniques, including Atomic Force Microscopy (AFM). At the time of his first enrolment in the study, he had normal Fasting Plasma Glucose (FPG) values, a BMI of 24.1, and no other symptoms of diabetes, including fatigue, high triglycerides, low HDL cholesterol, and altered inflammatory and corpuscular RBC indices. The subject reported no family history of diabetes, obesity, and cardiovascular diseases. Despite his apparently healthy conditions, the biomechanics of his RBCs was altered, showing increased values of stiffness and viscosity. More than 1 year after the mechanical measurements, the subject was admitted to the Operational Unit of Diabetology of the Policlinico Gemelli Hospital with high blood glucose and glycosylated hemoglobin (HbA1c) levels and diagnosed with type 1 diabetes (T1DM). Here, we show these data, and we discuss the hypothesis that RBC mechanical properties could be sensitive to changes occurring during the pre-diabetic phase of T1DM.
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http://dx.doi.org/10.3389/fbioe.2020.569978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552738PMC
September 2020

Enhanced Chemotherapy for Glioblastoma Multiforme Mediated by Functionalized Graphene Quantum Dots.

Materials (Basel) 2020 Sep 17;13(18). Epub 2020 Sep 17.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, 00185 Roma, Italy.

Glioblastoma is the most aggressive and lethal brain cancer. Current treatments involve surgical resection, radiotherapy and chemotherapy. However, the life expectancy of patients with this disease remains short and chemotherapy leads to severe adverse effects. Furthermore, the presence of the blood-brain barrier (BBB) makes it difficult for drugs to effectively reach the brain. A promising strategy lies in the use of graphene quantum dots (GQDs), which are light-responsive graphene nanoparticles that have shown the capability of crossing the BBB. Here we investigate the effect of GQDs on U87 human glioblastoma cells and primary cortical neurons. Non-functionalized GQDs (NF-GQDs) demonstrated high biocompatibility, while dimethylformamide-functionalized GQDs (DMF-GQDs) showed a toxic effect on both cell lines. The combination of GQDs and the chemotherapeutic agent doxorubicin (Dox) was tested. GQDs exerted a synergistic increase in the efficacy of chemotherapy treatment, specifically on U87 cells. The mechanism underlying this synergy was investigated, and it was found that GQDs can alter membrane permeability in a manner dependent on the surface chemistry, facilitating the uptake of Dox inside U87 cells, but not on cortical neurons. Therefore, experimental evidence indicates that GQDs could be used in a combined therapy against brain cancer, strongly increasing the efficacy of chemotherapy and, at the same time, reducing its dose requirement along with its side effects, thereby improving the life quality of patients.
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http://dx.doi.org/10.3390/ma13184139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560355PMC
September 2020

Graphene Quantum Dots' Surface Chemistry Modulates the Sensitivity of Glioblastoma Cells to Chemotherapeutics.

Int J Mol Sci 2020 Aug 31;21(17). Epub 2020 Aug 31.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Recent evidence has shown that graphene quantum dots (GQDs) are capable of crossing the blood-brain barrier, the barrier that reduces cancer therapy efficacy. Here, we tested three alternative GQDs' surface chemistries on two neural lineages (glioblastoma cells and mouse cortical neurons). We showed that surface chemistry modulates GQDs' biocompatibility. When used in combination with the chemotherapeutic drug doxorubicin, GDQs exerted a synergistic effect on tumor cells, but not on neurons. This appears to be mediated by the modification of membrane permeability induced by the surface of GQDs. Our findings highlight that GQDs can be adopted as a suitable delivery and therapeutic strategy for the treatment of glioblastoma, by both directly destabilizing the cell membrane and indirectly increasing the efficacy of chemotherapeutic drugs.
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http://dx.doi.org/10.3390/ijms21176301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503375PMC
August 2020

Characterization of an inorganic scintillator for small-field dosimetry in MR-guided radiotherapy.

J Appl Clin Med Phys 2020 Sep 25;21(9):244-251. Epub 2020 Aug 25.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Introduction: Aim of this study is to dosimetrically characterize a new inorganic scintillator designed for magnetic resonance-guided radiotherapy (MRgRT) in the presence of 0.35 tesla magnetic field (B).

Methods: The detector was characterized in terms of signal to noise ratio (SNR), reproducibility, dose linearity, angular response, and dependence by energy, field size, and B orientation using a 6 MV magnetic resonance (MR)-Linac and a water tank. Field size dependence was investigated by measuring the output factor (OF) at 1.5 cm. The results were compared with those measured using other detectors (ion chamber and synthetic diamond) and those calculated using a Monte Carlo (MC) algorithm. Energy dependence was investigated by acquiring a percentage depth dose (PDD) curve at two field sizes (3.32 × 3.32 and 9.96 × 9.96 cm ) and repeating the OF measurements at 5 and 10 cm depths.

Results: The mean SNR was 116.3 ± 0.6. Detector repeatability was within 1%, angular dependence was <2% and its response variation based on the orientation with respect to the B lines was <1%. The detector has a temporal resolution of 10 Hz and it showed a linear response (R  = 1) in the dose range investigated. All the OF values measured at 1.5 cm depth using the scintillator are in accordance within 1% with those measured with other detectors and are calculated using the MC algorithm. PDD values are in accordance with MC algorithm only for 3.32 × 3.32 cm field. Numerical models can be applied to compensate for energy dependence in case of larger fields.

Conclusion: The inorganic scintillator in the present form can represent a valuable detector for small-field dosimetry and periodic quality controls at MR-Linacs such as dose stability, OFs, and dose linearity. In particular, the detector can be effectively used for small-field dosimetry at 1.5 cm depth and for PDD measurements if the field dimension of 3.32 × 3.32 cm is not exceeded.
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http://dx.doi.org/10.1002/acm2.13012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497936PMC
September 2020

A field strength independent MR radiomics model to predict pathological complete response in locally advanced rectal cancer.

Radiol Med 2021 Mar 24;126(3):421-429. Epub 2020 Aug 24.

Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy.

Purpose: Aim of this study was to develop a generalised radiomics model for predicting pathological complete response after neoadjuvant chemo-radiotherapy in locally advanced rectal cancer patients using pre-CRT T2-weighted images acquired at a 1.5 T and a 3 T scanner.

Methods: In two institutions, 195 patients were scanned: 136 patients were scanned on a 1.5 T MR scanner, 59 patients on a 3 T MR scanner. Gross tumour volumes were delineated on the MR images and 496 radiomic features were extracted, applying the intensity-based (IB) filter. Features were standardised with Z-score normalisation and an initial feature selection was carried out using Wilcoxon-Mann-Whitney test: The most significant features at 1.5 T and 3 T were selected as main features. Several logistic regression models combining the main features with a third one selected by those resulting significant were elaborated and evaluated in terms of area under curve (AUC). A tenfold cross-validation was repeated 300 times to evaluate the model robustness.

Results: Three features were selected: maximum fractal dimension with IB = 0-50, energy and grey-level non-uniformity calculated on the run-length matrix with IB = 0-50. The AUC of the model applied to the whole dataset after cross-validation was 0.72, while values of 0.70 and 0.83 were obtained when 1.5 T and 3 T patients were considered, respectively.

Conclusions: The model elaborated showed good performance, even when data from patients scanned on 1.5 T and 3 T were merged. This shows that magnetic field intensity variability can be overcome by means of selecting appropriate image features.
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http://dx.doi.org/10.1007/s11547-020-01266-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937600PMC
March 2021

External Validation of Early Regression Index (ERI) as Predictor of Pathologic Complete Response in Rectal Cancer Using Magnetic Resonance-Guided Radiation Therapy.

Int J Radiat Oncol Biol Phys 2020 12 3;108(5):1347-1356. Epub 2020 Aug 3.

Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy.

Purpose: Tumor control probability (TCP)-based early regression index (ERI) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERI in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels.

Methods And Materials: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERI was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERI with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index.

Results: Fourteen patients showed pCR. ERI correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERI results are robust with respect to interobserver variability (intraclass correlation index = 0.99).

Conclusions: This study confirmed the validity and the robustness of ERI as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.2323DOI Listing
December 2020

Graphene Oxide-Linezolid Combination as Potential New Anti-Tuberculosis Treatment.

Nanomaterials (Basel) 2020 Jul 22;10(8). Epub 2020 Jul 22.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.

Global pandemic management represents a serious issue for health systems. In some cases, repurposing of existing medications might help find compounds that have the unexpected potential to combat microorganisms. In the same way, changing cell-drug interaction by nanotechnology could represent an innovative strategy to fight infectious diseases. Tuberculosis (TB) remains one of the most alarming worldwide infectious diseases and there is an urgent need for new drugs and treatments, particularly for the emergence and spread of drug-resistant () strains. New nanotechnologies based on carbon nanomaterials are now being considered to improve anti-TB treatments, and graphene oxide (GO) showed interesting properties as an anti-TB drug. GO, which preferentially accumulates in the lungs and is degraded by macrophagic peroxidases, can trap and in a dose-dependent manner, reducing the entry of bacilli into macrophages. In this paper, combinations of isoniazid (INH), amikacin (AMK) and linezolid (LZD) and GO anti-mycobacterial properties were evaluated against H37Rv by using a checkerboard assay or an in vitro infection model. Different GO effects have been observed when incubated with INH, AMK or LZD. Whereas the INH and AMK anti-mycobacterial activities were blocked by GO co-administration, the LZD bactericidal effect increased in combination with GO. GO-LZD significantly reduced extracellular mycobacteria during infection and was able to kill internalized bacilli. GO-LZD co-administration is potentially a new promising anti-TB treatment at the forefront in fighting emerging antibiotic-resistant strains where LZD administration is suggested. This innovative pharmacological approach may lead to reduced treatment periods and decreased adverse effects. More importantly, we demonstrate how nanomaterials-drugs combinations can represent a possible strategy to quickly design drugs for pandemics treatment.
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http://dx.doi.org/10.3390/nano10081431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466666PMC
July 2020

An evaluation of the objectivity and reproducibility of shear wave elastography in estimating the post-mortem interval: a tissue biomechanical perspective.

Int J Legal Med 2020 Sep 17;134(5):1939-1948. Epub 2020 Jul 17.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Cadaveric rigidity-also referred to as rigor mortis-is a valuable source of information for estimating the time of death, which is a fundamental and challenging task in forensic sciences. Despite its relevance, assessing the level of cadaveric rigidity still relies on qualitative and often subjective observations, and the development of a more quantitative approach is highly demanded. In this context, ultrasound shear wave elastography (US SWE) appears to be a particularly well-suited technique for grading cadaveric rigidity, as it allows non-invasive quantification of muscle stiffness in terms of Young's modulus (E), which is a widely used parameter in tissue biomechanics. In this pilot study, we measured, for the first time in the literature, changes in the mechanical response of muscular tissues from 0 to 60 h post-mortem (hpm) using SWE, with the aim of investigating its applicability to forensic practice. For this purpose, 26 corpses were included in the study, and the muscle mechanical response was measured at random times in the 0-60 hpm range. Despite the preliminary nature of this study, our data indicate a promising role of SWE in the quantitative determination of cadaveric rigidity, which is still currently based on qualitative and semiquantitative methods. A more in-depth study is required to confirm SWE applicability in this field in order to overcome some of the inherent limitations of the present work, such as the rather low number of cases and the non-systematic approach of the measurements.
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http://dx.doi.org/10.1007/s00414-020-02370-5DOI Listing
September 2020

Reliability of ITV approach to varying treatment fraction time: a retrospective analysis based on 2D cine MR images.

Radiat Oncol 2020 Jun 12;15(1):152. Epub 2020 Jun 12.

Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli,8, 00168, Rome, Italia.

Background: Internal Target Volume (ITV) is one of the most common strategies to passively manage tumour motion in Radiotherapy (RT). The reliability of this approach is based on the assumption that the tumour motion estimated during pre-treatment 4D Computed Tomography (CT) acquisition is representative of the motion during the whole RT treatment. With the introduction of Magnetic Resonance-guided RT (MRgRT), it has become possible to monitor tumour motion during the treatment and verify this assumption. Aim of this study was to investigate the reliability of the ITV approach with respect to the treatment fraction time (TFT) in abdominal and thoracic lesions.

Methods: A total of 12 thoracic and 15 abdominal lesions was analysed. Before treatment, a 10-phase 4DCT was acquired and ITV margins were estimated considering the envelope of the lesion contoured on the different 4DCT phases. All patients underwent MRgRT treatment in free-breathing, monitoring the tumour position on a sagittal plane with 4 frames per second (sec). ITV margins were projected on the tumour trajectory and the percentage of treatment time in which the tumour was inside the ITV (%TT) was measured to varying of TFT. The ITV approach was considered moderately reliable when %TT ≥ 90% and strongly reliable when %TT ≥ 95%. Additional ITV margins required to achieve %TT ≥ 95% were also calculated.

Results: In the analysed cohort of patients, ITV strategy can be considered strongly reliable only for lung lesions with TFT ≤ 7 min (min). The ITV strategy can be considered only moderately reliable for abdominal lesions, and additional margins are required to obtain %TT ≥ 95%. Considering a TFT ≤ 4 min, additional margins of 2 mm in cranio-caudal (CC) and 1 mm in antero-posterior (AP) are suggested for pancreatic lesions, 3 mm in CC and 2 mm in AP for renal and liver ones.

Conclusions: On the basis of the analysed cases, the ITV approach appears to be reliable in the thorax, while it results more challenging in the abdomen, due to the higher uncertainty in ITV definition and to the observed larger intra and inter-fraction motion variability. The addition of extra margins based on the TFT may represent a valid tool to compensate such limitations.
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http://dx.doi.org/10.1186/s13014-020-01530-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291491PMC
June 2020

Graphene Oxide Nano-Concentrators Selectively Modulate RNA Trapping According to Metal Cations in Solution.

Front Bioeng Biotechnol 2020 25;8:421. Epub 2020 May 25.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.

With recent advances in nanotechnology, graphene nanomaterials are being translated to applications in the fields of biosensing, medicine, and diagnostics, with unprecedented power. Graphene is a carbon allotrope derived from graphite exfoliation made of an extremely thin honeycomb of sp2 hybridized carbons. In comparison with the bulk materials, graphene and its water-soluble derivative graphene oxide have a smaller size suitable for diagnostic platform miniaturization as well as high surface area and consequently loading of a large number of biological probes. In this work, we propose a nanotechnological method for concentrating total RNA solution and/or enriching small RNA molecules. To this aim, we exploited the unique trapping effects of GO nanoflakes in the presence of divalent cations (i.e., calcium and magnesium) that make it flocculate and precipitate, forming complex meshes that are positively charged. Here, we demonstrated that GO traps can concentrate nucleic acids in the presence of divalent cations and that small RNAs can be selectively released from GO-magnesium traps. GO nano-concentrators will allow better analytical performance with samples available in small amounts and will increase the sensitivity of sequencing platforms by short RNA selection.
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http://dx.doi.org/10.3389/fbioe.2020.00421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261913PMC
May 2020

Graphene-based scaffolds for tissue engineering and photothermal therapy.

Nanomedicine (Lond) 2020 06 8;15(14):1411-1417. Epub 2020 Jun 8.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Roma, Italy.

Researchers have been creating 3D replicas of damaged tissues for millions of patients by using innovative biomaterials. While these scaffolds have regenerative properties, it would be beneficial if they could be utilized for local therapies, such as for cancer treatment. This report discusses the main advances in graphene scaffold design for near-infrared (NIR) photothermal therapy (PTT). NIR-PTT is a promising alternative for cancer cell killing, mediated by an increase of temperature due to NIR light-absorbers delivered to the tumor proximity. Graphene is a bidimensional material largely exploited in nanomedicine for its unique properties, such as high growth factor loading, which induces cell differentiation and its capacity to absorb NIR light. Here we cover aspects of future research in multifunctional graphene implants for cancer therapy and tissue regeneration.
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http://dx.doi.org/10.2217/nnm-2020-0050DOI Listing
June 2020

A time-dependent study of nano-mechanical and ultrastructural properties of internal limiting membrane under ocriplasmin treatment.

J Mech Behav Biomed Mater 2020 10 18;110:103853. Epub 2020 May 18.

Istituto di Oftalmologia, Università Cattolica del Sacro Cuore, Roma, Italy.

Vitreomacular traction (VMT) syndrome has only been surgically treated for a long time. Recently, enzymatic vitreolysis with ocriplasmin has emerged as a possible option to release VMT and, in some cases, close full thickness macular holes (FTMHs). Despite its clinical relevance, gathering information about the ocriplasmin-induced alterations of the Inner Limiting Membrane (ILM) of the retina in a clinical study is a complex task, mainly because of the inter-individual variability among patients. To obtain more insights into the mechanism underlying the drug action, we studied in-vitro the mechanical and morphological changes of the ILM using Atomic Force Microscopy (AFM). To this aim, we measured the ILM average Young's modulus (YM), hysteresis (H) and adhesion work (A) over time under ocriplasmin treatment. Our data unveil a time-dependent increase in the membrane YM of 19% of its initial value, along with changes in its adhesive and dissipative behavior. Such modifications well correlate with the morphological alterations detected in the AFM imaging mode. Taken all together, the results here presented provide more insights into the mechanism underlying the ocriplasmin action in-vivo, suggesting that it is only able to alter the top-most layer of the vitreal side of the membrane, not compromising the inner ILM structure.
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http://dx.doi.org/10.1016/j.jmbbm.2020.103853DOI Listing
October 2020

Machine-learning assisted confocal imaging of intracellular sites of triglycerides and cholesteryl esters formation and storage.

Anal Chim Acta 2020 Jul 3;1121:57-66. Epub 2020 May 3.

Fondazione Policlinico Universitario A. Gemelli IRCSS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica Del Sacro Cuore, Rome, Italy. Electronic address:

All living systems are maintained by a constant flux of metabolic energy and, among the different reactions, the process of lipids storage and lipolysis is of fundamental importance. Current research has focused on the investigation of lipid droplets (LD) as a powerful biomarker for the early detection of metabolic and neurological disorders. Efforts in this field aim at increasing selectivity for LD detection by exploiting existing or newly synthesized probes. However, LD constitute only the final product of a complex series of reactions during which fatty acids are transformed into triglycerides and cholesterol is transformed in cholesteryl esters. These final products can be accumulated in intracellular organelles or deposits other than LD. A complete spatial mapping of the intracellular sites of triglycerides and cholesteryl esters formation and storage is, therefore, crucial to highlight any potential metabolic imbalance, thus predicting and counteracting its progression. Here, we present a machine learning assisted, polarity-driven segmentation which enables to localize and quantify triglycerides and cholesteryl esters biosynthesis sites in all intracellular organelles, thus allowing to monitor in real-time the overall process of the turnover of these non-polar lipids in living cells. This technique is applied to normal and differentiated PC12 cells to test how the level of activation of biosynthetic pathways changes in response to the differentiation process.
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http://dx.doi.org/10.1016/j.aca.2020.04.076DOI Listing
July 2020

Unravelling the Potential of Graphene Quantum Dots in Biomedicine and Neuroscience.

Int J Mol Sci 2020 May 25;21(10). Epub 2020 May 25.

Department of Neuroscience, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.

Quantum dots (QDs) are semiconducting nanoparticles that have been gaining ground in various applications, including the biomedical field, thanks to their unique optical properties. Recently, graphene quantum dots (GQDs) have earned attention in biomedicine and nanomedicine, thanks to their higher biocompatibility and low cytotoxicity compared to other QDs. GQDs share the optical properties of QD and have proven ability to cross the blood-brain barrier (BBB). For this reason, GQDs are now being employed to deepen our knowledge in neuroscience diagnostics and therapeutics. Their size and surface chemistry that ease the loading of chemotherapeutic drugs, makes them ideal drug delivery systems through the bloodstream, across the BBB, up to the brain. GQDs-based neuroimaging techniques and theranostic applications, such as photothermal and photodynamic therapy alone or in combination with chemotherapy, have been designed. In this review, optical properties and biocompatibility of GQDs will be described. Then, the ability of GQDs to overtake the BBB and reach the brain will be discussed. At last, applications of GQDs in bioimaging, photophysical therapies and drug delivery to the central nervous system will be considered, unraveling their potential in the neuroscientific field.
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http://dx.doi.org/10.3390/ijms21103712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279214PMC
May 2020

3D Graphene Scaffolds for Skeletal Muscle Regeneration: Future Perspectives.

Front Bioeng Biotechnol 2020 5;8:383. Epub 2020 May 5.

Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.

Although skeletal muscle can regenerate after injury, in chronic damages or in traumatic injuries its endogenous self-regeneration is impaired. Consequently, tissue engineering approaches are promising tools for improving skeletal muscle cells proliferation and engraftment. In the last decade, graphene and its derivates are being explored as novel biomaterials for scaffolds production for skeletal muscle repair. This review describes 3D graphene-based materials that are currently used to generate complex structures able not only to guide cell alignment and fusion but also to stimulate muscle contraction thanks to their electrical conductivity. Graphene is an allotrope of carbon that has indeed unique mechanical, electrical and surface properties and has been functionalized to interact with a wide range of synthetic and natural polymers resembling native musculoskeletal tissue. More importantly, graphene can stimulate stem cell differentiation and has been studied for cardiac, neuronal, bone, skin, adipose, and cartilage tissue regeneration. Here we recapitulate recent findings on 3D scaffolds for skeletal muscle repairing and give some hints for future research in multifunctional graphene implants.
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http://dx.doi.org/10.3389/fbioe.2020.00383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214535PMC
May 2020

Inhibition of Transglutaminase 2 as a Potential Host-Directed Therapy Against .

Front Immunol 2019 24;10:3042. Epub 2020 Jan 24.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Host-directed therapies (HDTs) are emerging as a potential valid support in the treatment of drug-resistant tuberculosis (TB). Following our recent report indicating that genetic and pharmacological inhibition of transglutaminase 2 (TG2) restricts () replication in macrophages, we aimed to investigate the potentials of the TG2 inhibitors cystamine and cysteamine as HDTs against TB. We showed that both cysteamine and cystamine restricted replication in infected macrophages when provided at equimolar concentrations and did not exert any antibacterial activity when administered directly on cultures. Interestingly, infection of differentiated THP-1 mRFP-GFP-LC3B cells followed by the determination of the autophagic intermediates pH distribution (AIPD) showed that cystamine inhibited the autophagic flux while restricting replication. Moreover, both cystamine and cysteamine had a similar antimicrobial activity in primary macrophages infected with a panel of clinical strains belonging to different phylogeographic lineages. Evaluation of cysteamine and cystamine activity in the human model of granuloma-like structures (GLS) further confirmed the ability of these drugs to restrict replication and to reduce the size of GLS. The antimicrobial activity of the TG2 inhibitors synergized with a second-line anti-TB drug as amikacin in human monocyte-derived macrophages and in the GLS model. Overall, the results of this study support the potential usefulness of the TG2-inhibitors cysteamine and cystamine as HDTs against TB.
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http://dx.doi.org/10.3389/fimmu.2019.03042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992558PMC
November 2020

Altered mitochondrial function in cells carrying a premutation or unmethylated full mutation of the FMR1 gene.

Hum Genet 2020 Feb 9;139(2):227-245. Epub 2020 Jan 9.

Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito 1, 00168, Roma, Italy.

Fragile X-related disorders are due to a dynamic mutation of the CGG repeat at the 5' UTR of the FMR1 gene, coding for the RNA-binding protein FMRP. As the CGG sequence expands from premutation (PM, 56-200 CGGs) to full mutation (> 200 CGGs), FMRP synthesis decreases until it is practically abolished in fragile X syndrome (FXS) patients, mainly due to FMR1 methylation. Cells from rare individuals with no intellectual disability and carriers of an unmethylated full mutation (UFM) produce slightly elevated levels of FMR1-mRNA and relatively low levels of FMRP, like in PM carriers. With the aim of clarifying how UFM cells differ from CTRL and FXS cells, a comparative proteomic approach was undertaken, from which emerged an overexpression of SOD2 in UFM cells, also confirmed in PM but not in FXS. The SOD2-mRNA bound to FMRP in UFM more than in the other cell types. The high SOD2 levels in UFM and PM cells correlated with lower levels of superoxide and reactive oxygen species (ROS), and with morphological anomalies and depolarization of the mitochondrial membrane detected through confocal microscopy. The same effect was observed in CTRL and FXS after treatment with MC2791, causing SOD2 overexpression. These mitochondrial phenotypes reverted after knock-down with siRNA against SOD2-mRNA and FMR1-mRNA in UFM and PM. Overall, these data suggest that in PM and UFM carriers, which have high levels of FMR1 transcription and may develop FXTAS, SOD2 overexpression helps to maintain low levels of both superoxide and ROS with signs of mitochondrial degradation.
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http://dx.doi.org/10.1007/s00439-019-02104-7DOI Listing
February 2020

On the accuracy of bulk synthetic CT for MR-guided online adaptive radiotherapy.

Radiol Med 2020 Feb 8;125(2):157-164. Epub 2019 Oct 8.

Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.

Purpose: MR-guided radiotherapy (MRgRT) relies on the daily assignment of a relative electron density (RED) map to allow the fraction specific dose calculation. One approach to assign the RED map consists of segmenting the daily magnetic resonance image into five different density levels and assigning a RED bulk value to each level to generate a synthetic CT (sCT). The aim of this study is to evaluate the dose calculation accuracy of this approach for applications in MRgRT.

Methods: A planning CT (pCT) was acquired for 26 patients with abdominal and pelvic lesions and segmented in five levels similar to an online approach: air, lung, fat, soft tissue and bone. For each patient, the median RED value was calculated for fat, soft tissue and bone. Two sCTs were generated assigning different bulk values to the segmented levels on pCT: The sCT uses the RED values recommended by ICRU46, and the sCT uses the median patient-specific RED values. The same treatment plan was calculated on two the sCTs and the pCT. The dose calculation accuracy was investigated in terms of gamma analysis and dose volume histogram parameters.

Results: Good agreement was found between dose calculated on sCTs and pCT (gamma passing rate 1%/1 mm equal to 91.2% ± 6.9% for sCT and 93.7% ± 5.3% b or sCT). The mean difference in estimating V95 (PTV) was equal to 0.2% using sCT and 1.2% using sCT, respect to pCT values CONCLUSIONS: The bulk sCT guarantees a high level of dose calculation accuracy also in presence of magnetic field, making this approach suitable to MRgRT. This accuracy can be improved by using patient-specific RED values.
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http://dx.doi.org/10.1007/s11547-019-01090-0DOI Listing
February 2020

Carbon nanomaterials: a new way against tuberculosis.

Expert Rev Med Devices 2019 Oct 30;16(10):863-875. Epub 2019 Sep 30.

Fondazione Policlinico Universitario A. Gemelli, IRCCS , Roma , Italy.

: Tuberculosis (TB) remains one of the most alarming worldwide infectious diseases primarily in low-income countries, where the infection shows a higher and unvaried prevalence. In the last years, the emergence and spread of () strains resistant to first-line anti-TB drugs are the cause of major concern and prompted the implementation of new treatments, including the development of new drugs and the repurposing of old ones. : In this review, we discuss solutions against TB based on nanomaterials (NMTs), alone or combined with current anti-TB drugs. We will summarize drug delivery platforms tested in or models and their activity against mycobacteria. We will describe how the new nanotechnologies based on carbon nanomaterials, like carbon nanotubes and graphene oxide are now facing the panorama of the medical fight against TB. : We foresee that in the next decade carbon nanomaterials will be at the forefront in fighting emerging antibiotic-resistant strains by shortening treatment periods, reducing adverse effects and mitigating antibiotic use. However, toxicity and biodegradation studies should be done prior to the clinical translation of carbon nanomaterials.
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http://dx.doi.org/10.1080/17434440.2019.1671820DOI Listing
October 2019