Aging promotes neoplastic disease through effects on the tissue microenvironment

A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes

Chemical composition and biological activity of the volatile extracts of Achillea millefolium.

In this study, flowering aerial parts of wild Achillea millefolium growing on the Mediterranean coast (Sardinia Island, Italy) and on the Atlantic coast (Portugal- Serra de Montemuro) were used as a matrix for supercritical extraction of volatile oil with CO2 (SFE). The collected extracts were analyzed by GC-FID and GC-MS methods and their composition were compared with that of the essential oil isolated by hydrodistillation. A strong chemical variability in essential oils depending on the origin of the samples was observed. The results showed the presence of two type oils. The Italian volatile extracts (SFE and essential oil) are predominantly composed by α-asarone (25.6-33.3%, in the SFE extract and in the HD oil, respectively), β-bisabolene (27.3-16.6%) and α-pinene (10.0-17.0%); whereas the main components of the Portuguese extracts are trans-thujone (31.4-29.0%), trans-crhysanthenyl acetate (19.8-15.8%) and β-pinene (1.2-11.1%). The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oils against Candida albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes, T. mentagrophytes var. interdigitale, T. verrucosum, Microsporum canis, M. gypseum, Epidermophyton floccosum, Aspergillus niger, A. fumigatus and A. flavus. The oils showed the highest activity against dermatophyte strains, with MIC values ranging from 0.32-1.25 μL mL−1

Solid-State Nuclear Magnetic Resonance of Triple-Cation Mixed-Halide Perovskites

Mixed-cation lead mixed-halide perovskites are the best candidates for perovskite-based photovoltaics, thanks to their higher efficiency and stability compared to the single-cation single-halide parent compounds. TripleMix (Cs0.05MA0.14FA0.81PbI2.55Br0.45 with FA = formamidinium and MA = methylammonium) is one of the most efficient and stable mixed perovskites for single-junction solar cells. The microscopic reasons why triplecation perovskites perform so well are still under debate. In this work, we investigated the structure and dynamics of TripleMix by exploiting multinuclear solid-state nuclear magnetic resonance (SSNMR), which can provide this information at a level of detail not accessible by other techniques. 133Cs, 13C, 1 H, and 207Pb SSNMR spectra confirmed the inclusion of all ions in the perovskite, without phase segregation. Complementary measurements showed a peculiar longitudinal relaxation behavior for the 1 H and 207Pb nuclei in TripleMix with respect to single-cation single-halide perovskites, suggesting slower dynamics of both organic cations and halide anions, possibly related to the high photovoltaic performances

Biological Assays and Chemical Composition of Volatile Oils of Bupleurum fruticosum L. (Apiaceae)

The composition of supercritical CO 2 extracts and essential oils obtained by hydrodistillation of Bupleurum fruticosum L., growing spontaneously in Italy and Portugal, and its antifungal activity is reported. The collected extracts were analyzed by GC-FID and GC-MS methods. The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oils against Candida albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes, Microsporum canis, M. gypseum, Epidermophyton floccosum, Aspergillus niger, A. fumigatus and A. flavus

Periapical status in patients affected by osteoporosis: A retrospective clinical study

Objectives: To assess the periapical status in patients with osteoporosis (OP) treated with denosumab (D), bisphosphonates (BPs), or not on medication, and to understand if these conditions influence the prevalence and the progression of apical periodontitis (AP).Material and Methods: Seventy-six patients with OP alone or treated with D, or BPs, formed the study group (O), and those from 76 patients matched for age and sex, without diseases, and not taking medications, constituted the control (C) in this retrospective case-control study. The data from the complete clinical and radiographic examination, medical history, decayed, missing, and filled teeth (DMFT), and periapical index score (PAI) were recorded for each patient. Wilcoxon rank test, chi(2), and Student's t test were used as appropriate.Results: The prevalence of AP was similar in O and C. Furthermore, AP was significantly more frequent in root canal-treated teeth in O patients (p = .03).Conclusions: OP does not appear to be associated with the development of AP. Moreover, the increased prevalence of AP in root canal-treated teeth in O patients highlights a possible relationship between the healing dynamics of the disease post-therapy and the patients' medication. A larger sample is needed to confirm these findings

Isolation of the Volatile Oil from Satureja thymbra by Supercritical Carbon Dioxide Extraction: Chemical Composition and Biological Activity:

Satureja thymbra L. is well known in Italy by the popular name of "Santoreggia sarda". It grows only in Sardinia and nowadays it is restricted to the slope of the Colle San Michele in Cagliari. The composition of the aromatic extracts obtained by supercritical CO2 and by hydrodistillation and their antifungal activity is reported. The collected extracts were analyzed by GC-FID and GC-MS methods. No significant differences were observed in the composition of the volatile extracts depending on the extraction method. The results showed the presence of thymol, γ-terpinene, β-caryophyllene, p-cymene, carvacrol and borneol as main components. The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oils against Candida albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, T. mentagrophytes, T. mentagrophytes var. interdigitale, Trichophyton rubrum, T. verrucosum, Microsporum canis, M. gypseum, Epidermophyton floccosum, Aspergillus niger, A. fumigatus and A. flavus. The volatile extracts revealed a wide-spectrum antifungal activity. They were fungicidal and similarly potent against yeasts, dermatophyte and Aspergillus stains, with MICs ranging from 0.16 to 0.32 μL.mL−1

Qualitative and Semiquantitative Parameters of 18F-FDG-PET/CT as Predictors of Malignancy in Patients with Solitary Pulmonary Nodule

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy

Human Enterovirus B: Selective Inhibition by Quinoxaline Derivatives and Bioinformatic RNA-Motif Identification as New Targets

The Enterovirus genus includes many viruses that are pathogenic in humans, including Coxsackie viruses and rhinoviruses, as well as the emerging enteroviruses D68 and A71. Currently, effective antiviral agents are not available for the treatment or prevention of enterovirus infections, which remain an important threat to public health. We recently identified a series of quinoxaline derivatives that were provento be potent inhibitors of coxsackievirus B5, the most common and a very important human pathogen belonging to the enterovirus genus. We have shown how most active derivatives interfere with the earliest stages of viral replication, blocking infection. Considering the broad antiviral spectrum, a very attractive property for an antiviral drug, we aimed to investigate the antiviral activity of the most promising compounds against other Enterovirus species. Here, we investigated the susceptibility of a panel of representatives of Enterovirus genus (enterovirus A71, belonging to A species; coxsackieviruses B4 and B3;echovirus 9, belonging to B species; and enterovirus D68, belonging to D species) to quinoxaline inhibitors. We also tested cytotoxicity and selectivity indices of the selected compounds, as well as their effects on virus yield.We also investigated their potential mechanism of action by a time course assay. In addition, a bioinformatic analysis was carried out to discover potential new conserved motifs in CVB3 and CVB4 compared to the other enterovirus species that can be used as new targets

Clot characterization by multidisciplinary approach: biochemical and imaging parameters in a hypocoagulative setting. A pilot study.

Background: Clot characterization is, to the present days, a multimodal approach: scanning the clot by electron microscopy (SEM) is helpful for the visualization of fibrin structure along with laboratory parameters such as the clot waveform analysis (CWA) and thrombin generation in different settings of clot abnormalities. This study aimed to assess whether the coagulative parameters were consistent with the clot images texture acquired by SEM, and therefore to propose a more generalist and integrative approach to clots classification.Design and Methods: In this pilot study, the examined population consists of eight healthy subjects, seven patients affected by Acquired Hemophilia A (AHA) and seven patients treated with Vitamin K Antagonists (VKAs), similar for age and gender. We studied the velocity and acceleration (1st and 2nd derivative of the aPTT) of clot formation (CWA), the thrombin generation, and the clots' scanning by SEM. Images acquired with SEM were then analyzed with the MATLAB software with the "Texture Analysis" methods to perform classification. Among the various texture parameters, we reported Contrast and Energy.Results: Significant differences among healthy subjects, patients with AHA and those treated with VKAs were detected for the coagulative parameters. We found no differences between VKAs and AHA patients. Contrast and energy highlighted a significant difference among the three groups in agreement with the laboratory's parameters. We found no significant differences between VKAs and AHA patients.Conclusions: The use of SEM, CWA and thrombin generation parameters may be a starting point for studies aimed to demonstrate the general characteristics of clot formation in different clinical conditions with a multiparametric approach

Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study

Background: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. Methods: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. Results: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). Conclusions: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease