Oleocanthal Exerts Antitumor Effects on Human Liver and Colon Cancer Cells Through ROS Generation

The beneficial health properties of the Mediterranean diet are well recognized. The principle source of fat in Mediterranean diet is extra-virgin olive oil (EVOO). Oleocanthal (OC) is a naturally occurring minor phenolic compound isolated from EVOO, which has shown a potent anti-inflammatory activity, by means of its ability to inhibit the cyclooxygenase (COX) enzymes COX-1 and COX-2. A large body of evidence indicates that phenols exhibit anticancer activities. The aim of the present study was to evaluate the potential anticancer effects of OC in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) models. A panel of human HCC (HepG2, Huh7, Hep3B and PLC/PRF/5) and CRC (HT29, SW480) cell lines was used. Cells were treated with OC, and cell viability and apoptosis were evaluated. Compared with classical commercially available COX inhibitors (ibuprofen, indomethacin, nimesulide), OC was more effective in inducing cell growth inhibition in HCC and CRC cells. Moreover, OC inhibited colony for mation and i nduced ap optosis, as confirmed by PARP cleavage, activation of caspases 3/7 and chromatin condensation. OC treatment in a dose dependent-manner induced expression of \uce\ub3H2AX, a marker of DNA damage, increased intracellular ROS production and caused mitochondrial depolarization. Moreover, the effects of OC were suppressed by the ROS scavenger N-acetyl-L-cysteine. Finally, OC was not toxic in primary normal human hepatocytes. In conclusion, OC treatment was found to exert a potent anticancer activity against HCC and CRC cells. Taken together, our findings provide preclinical support of the chemotherapeutic potential of EVOO against cancer

A blended TROPOMI+GOSAT satellite data product for atmospheric methane using machine learning to correct retrieval biases

Satellite observations of dry-column methane mixing ratios (XCH4) from shortwave infrared (SWIR) solar backscatter radiation provide a powerful resource to quantify methane emissions in service of climate action. The TROPOspheric Monitoring Instrument (TROPOMI), launched in October 2017, provides global daily coverage at a 5.5 × 7 km2 (nadir) pixel resolution, but its methane retrievals can suffer from biases associated with SWIR surface albedo, scattering from aerosols and cirrus clouds, and across-track variability (striping). The Greenhouse gases Observing SATellite (GOSAT) instrument, launched in 2009, has better spectral characteristics and its methane retrieval is much less subject to biases, but its data density is 250 times sparser than TROPOMI. Here, we present a blended TROPOMI+GOSAT methane product obtained by training a machine learning (ML) model to predict the difference between TROPOMI and GOSAT co-located measurements, using only predictor variables included in the TROPOMI retrieval, and then applying the correction to the complete TROPOMI record from April 2018 to present. We find that the largest corrections are associated with coarse aerosol particles, high SWIR surface albedo, and across-track pixel index. Our blended product corrects a systematic difference between TROPOMI and GOSAT over water, and it features corrections exceeding 10 ppb over arid land, persistently cloudy regions, and high northern latitudes. It reduces the TROPOMI spatially variable bias over land (referenced to GOSAT data) from 14.3 to 10.4 ppb at a 0.25∘ × 0.3125∘ resolution. Validation with Total Carbon Column Observing Network (TCCON) ground-based column measurements shows reductions in variable bias compared with the original TROPOMI data from 4.7 to 4.4 ppb and in single-retrieval precision from 14.5 to 11.9 ppb. TCCON data are all in locations with a SWIR surface albedo below 0.4 (where TROPOMI biases tend to be relatively low), but they confirm the dependence of TROPOMI biases on SWIR surface albedo and coarse aerosol particles, as well as the reduction of these biases in the blended product. Fine-scale inspection of the Arabian Peninsula shows that a number of hotspots in the original TROPOMI data are removed as artifacts in the blended product. The blended product also corrects striping and aerosol/cloud biases in single-orbit TROPOMI data, enabling better detection and quantification of ultra-emitters. Residual coastal biases can be removed by applying additional filters. The ML method presented here can be applied more generally to validate and correct data from any new satellite instrument by reference to a more established instrument.</p

Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma.

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellular carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV co-infected patients show a higher prevalence of the low-producer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC

Association between single nucleotide polymorphisms in the COX-2, TNF-alpha and VEGF-A genes and susceptibility to hepatocellular carcinoma

Introduction: TNF-a, COX-2 and Vascular Endothelial Growth Factor (VEGFA) are mediators of inflammation and angiogenesis, all of them are abundantly produced in liver cirrhosis (LC). It was proposed that there is an association between single nucleotide polymorphisms (SNPs) and hepatocellular carcinoma (HCC). These allelic variants influence the transcriptional activity of these genes, and therefore the proteins levels. The VEGF-A pathway is a potential therapeutic target in HCC, and several anti-angiogenic agents have entered clinical trials in HCC. Aims: 1) To evaluate thè frequency of SNPs of COX-2, TNF-a and VEGF-A genes in patients with HCC vs LC patients and a control group (C). 2) To verify thè correlation between thè allelic variations and the risk of developing HCC tumors. Methods: DNA extracted from whole blood of C, HCC and LC patients (all from Sicily, Italy), was used for the evaluation of SNPs by the RFLP-PCR method. The SNPs analyzed were at position -1195 G>A in the promoter regions, of COX-2 (A allele is associated with higher levels of thè enzyme), at position -308 G>A in thè promoter regions of TNF-a genes (G allele is associated with lower levels of the cytokine), and at position +936 C>T in the coding region of VEGFA gene (T allele is associated with high levels of the growth factor). X2, Fisher exact tests were used for statistical analysis. Results: We obtained a significant difference only for the SNP +936 C>7 of VEGF-A gene. Results obtained are shown in the following table

Leaf Litter Decomposition and Nutrient-Release Characteristics of Several Willow Varieties Within Short-Rotation Coppice Plantations in Saskatchewan, Canada

Quantifying short-rotation coppice (SRC) willow leaf litter dynamics will improve our understanding of carbon (C) sequestration and nutrient cycling potentials within these biomass energy plantations and provide valuable data for model validation. The objective of this study was to quantify the decomposition rate constants (kBiomass) and decomposition limit values (LVBiomass), along with associated release rates (kNutrient) and release limits (LVNutrient) of nitrogen (N), phosphorus (P), potassium (K), sulphur (S), calcium (Ca), and magnesium (Mg) of leaf litter from several native and exotic willow varieties during an initial four-year rotation at four sites within Saskatchewan, Canada. The kBiomass, LVBiomass, kNutrient, and LVNutrient values varied among the willow varieties, sites, and nutrients, with average values of 1.7 year-1, 79 %, 0.9 year-1, and 83 %, respectively. Tissue N had the smallest kNutrient and LVNutrient values, while tissue K and Mg had the largest kNutrient and LVNutrient values, respectively. The leaf litter production varied among willow varieties and sites with an average biomass accumulation of 7.4 Mg ha-1 after the four-year rotation and associated C sequestration rate of 0.2 Mg C ha-1 yr-1. The average contribution of nutrients released from leaf litter decomposition during the four-year rotation to the plant available soil nutrient pool across varieties and sites was 22, 4, 47, 10, 112, and 18 kg ha-1 of N, P, K, S, Ca, and Mg, respectively. Principal component analysis identified numerous key relationships between the measured soil, plant tissue, climate and microclimate variables and observed willow leaf litter decomposition and nutrient release characteristics. Our findings support the contention that SRC willow leaf litter is capable of enhancing both soil organic C levels and supplementing soil nutrient availability over time