MR imaging of focal liver lesions: comparison between turbo spin-echo and conventional spin-echo pulse sequences

The aim of this study was to compare conventional spin-echo (CSE)T ₂-weighted (T2W) images with turbo spin-echo (TSE) T2W pulse sequences in their ability to detect focal liver lesions. Seventy-eight consecutive patients with focal liver lesions were entered into this study. All patients were imaged using the gradient-echo (GE) sequence with the breath-hold technique forT ₁-weighted (T1W) images, and CSE and TSE sequences for T2W images. Qualitative evaluation included lesion detection (number of lesions detected) and conspicuity (extent of visualization of lesional borders); quantitative evaluation included the signal-to-noise (S/N) ratio and the contrast-to-noise (C/N) ratio. TSE showed the best performance in terms of lesion detection; however, the difference between TSE and CSE was significant only in the case of benign cysts (p<0.01). Conspicuity was higher with TSE and CSE, and lower with GE. The S/N and C/N ratios of the two T2W sequences were also comparable, and better than those of GE. However, the combined use of GE and TSE resulted in improved lesion detection. The results show that, because the acquisition time is greatly reduced with TSE sequences, these should be considered as first-line approach to magnetic resonance imaging of the liver for the study of focal lesions.     

Synthesis, Molecular Characterization and Preliminary Antioxidant Activity Evaluation of Quercetin Fatty Esters

Quercetin shows interesting pharmacological effects, but its use in topical applications is limited by its low skin permeability and solubility. In this work, the synthesis of highly lipophilic quercetin esters with oleic, linoleic and linolenic acid useful as topical quercetin prodrugs is reported. Partial OH esterification is advisable to maintain the antioxidant activity of these compounds; tetraesters and triesters can be achieved by modulating the reaction conditions utilized for the total esterification of quercetin. The chemical structures of the esters were proven by spectroscopic techniques; quantum chemical NMR calculation were mandatory to unequivocally assign the free position in triesters. Finally, the antioxidant activity of all the synthesized compounds was determined by the 2,2-diphenyl-1-picryl-hydrazyl method and by 2,2-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) assay.     

Identification and quantification of cholesterol oxidation products in canned tuna

Cholesterol oxidation in tuna canned in brine was studied. Gas chromatography-mass spectrometry was used for the detection of the seven major cholesterol oxidation products originating from both direct and indirect oxidation. The total amount of cholesterol oxidation products in the analyzed samples varied considerably, ranging between 40 and 350 μg/g lipids, with the exception of an anomalous sample, that reached a 1600 μg/g level. The lipid content ranged between 0.5 and 1 g/100 g wet product. As most samples did not exceed 100 μg/g lipids, it is possible to assume that the total content of cholesterol oxidation products can be kept below this value if good manufacturing conditions are used, together with a careful choice of the best tuna cuts. The application of principal component analysis to the detected variables confirmed that 7-ketocholesterol is a useful index of the whole oxidation process.     

Luster Pottery from the Thirteenth Century to the Sixteenth Century: A Nanostructured Thin Metallic Film

Luster is a decorative metallic film that was applied on the surface of medieval glazed pottery. It can be obtained via the low-temperature (∼650°C), controlled reduction of copper and silver compounds. In this paper, we show that luster is a thin layered film (200–500 nm thick) that contains metallic spherical nanocrystals dispersed in a silicon-rich matrix and has a metal-free outermost glassy layer that is 10–20 nm thick. Silver nanocrystals seem to be separated from those of copper, forming aggregates 5–100 μm in diameter. This composite structure exhibits optical properties that are dependent on both the particle size and the matrix. Luster is indeed the first reproducible nanostructured thin metallic film that was made by humans.     

Synthesis,Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors

We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.     

Sex and Depot Differences in Palmitoleic Acid Content of Human Blood and Fat

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test–retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans.     

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.     

Role of NEU3 Overexpression in the Prediction of Efficacy of EGFR-Targeted Therapies in Colon Cancer Cell Lines

The epidermal growth factor receptor (EGFR), through the MAP kinase and PI3K-Akt-mTOR axis, plays a pivotal role in colorectal cancer (CRC) pathogenesis. The membrane-associated NEU3 sialidase interacts with and desialylates EGFR by promoting its dimerization and downstream effectors’ activation. Among the targeted therapies against EGFR, the monoclonal antibody cetuximab is active only in a subgroup of patients not carrying mutations in the MAP kinase pathway. In order to better understand the EGFR-NEU3 interplay and the mechanisms of pharmacological resistance, we investigated the role of NEU3 deregulation in cetuximab-treated CRC cell lines transiently transfected with NEU3 using Western blot analysis. Our results indicate that NEU3 overexpression can enhance EGFR activation only if EGFR is overexpressed, indicating the existence of a threshold for NEU3-mediated EGFR activation. This enhancement mainly leads to the constitutive activation of the MAP kinase pathway. Consequently, we suggest that the evaluation of NEU3 expression cannot entirely substitute the evaluation of EGFR because EGFR-negative cases cannot be stimulated by NEU3. Furthermore, NEU3-mediated hyperactivation of EGFR is counterbalanced by the administration of cetuximab, hypothesizing that a combined treatment of NEU3- and EGFR-targeted therapies may represent a valid option for CRC patients, which must be investigated in the future.     

AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations

Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials.