Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer

Role of Soluble Endothelial Cell–Selective Adhesion Molecule Biomarker in Albuminuria and Kidney Function Changes in Patients With Coronary Artery Disease

ObjectiveEndothelial dysfunction is a possible mechanism to explain the association between atherosclerosis and kidney disease. This study evaluated circulating soluble endothelial cell-selective adhesion molecule (sESAM), a marker of endothelial dysfunction, as a risk factor for kidney function decline and albuminuria.Approach and resultsIn the Heart and Soul Study, we measured sESAM from baseline serum samples and defined elevated levels of sESAM by the highest quartile (quartile 4 [Q4]: >65.4 ng/mL). We evaluated the associations of high sESAM with baseline estimated glomerular filtration rate (eGFR) and ratio of urine albumin to creatinine (ACR), and with longitudinal changes in eGFR and ACR. Among 990 participants with sESAM measurements, median sESAM was 54.5 ng/mL (interquartile range, 45.3-65.8). After multivariable adjustment, elevated levels of sESAM were strongly and independently associated with baseline reduced eGFR <60 mL/min per 1.73 m(2) (odds ratio [OR], 11.44; P<0.0001) and ACR ≥30 mg/g (OR, 5.23; P<0.0001). Associations of sESAM (Q4 versus quartile 1 [Q1]) with change in ACR (β=54.47; P<0.0001) were also significant after full adjustment. The association with change in eGFR (1.56%; P=0.0049) was not statistically significant after application of the Bonferroni correction for multiple markers. In unadjusted models, sESAM was associated with rapid kidney function loss, defined as 3% annual eGFR decline (OR, 2.28; P=0.0003), although this was attenuated by adjustment (OR, 2.11; P=0.0095).ConclusionssESAM is associated with albuminuria and reduced kidney function in both cross-sectional and longitudinal analyses. These findings implicate endothelial dysfunction as a potential contributor to the elevated kidney disease risk in persons with cardiovascular disease

Science Applied for the Investigation of Imperial Gate from Eighteenth Century Wooden Church of Nicula Monastery

Part of an indestructible component of any orthodox church, the Imperial Gates represent an important symbol in our cultural heritage. But in many cases the Imperial Gates from the wooden churches were damaged. In order to preserve and restore them, the scientific investigations of the Imperial Gate belonging to Nicula Monastery wooden church were performed by employing nondestructive and destructive methods. The wood essence was established, with its “health” status being investigated by FTIR (Fourier Transform Infrared) spectroscopy and DSC (Differential Scanning Calorimetry) thermal analysis. The painting materials employed by popular artists were determined by FTIR and XRF (X-ray fluorescence) spectroscopy as gypsum, calcite (rear background), lead white (Archangel Clothes), lead-minium (Archangel Clothes, leaf), iron oxide (Imperial Gate frame), malachite (green), Prussian blue (blue), orpiment (yellow), aliphatic, ester, and protein (probably egg yolk degradation products). Using similar colors as in the original artwork (resulting from the scientific investigation of the pigments) a 3D reconstruction has been performed. The restored Imperial Gates are placed in the old Nicula wooden church, being included into a tourist and religious circuit