The antioxidant and antifibrogenic effects of the glycosaminoglycans hyaluronic acid and chondroitin-4-sulphate in a subchronic rat model of carbon tetrachloride-induced liver fibrogenesis

Hepatic fibrosis involves the interplay of many factors including reactive oxygen species. Recent reports described antioxidant properties of glycosaminoglycans (GAGs). Since several findings have shown that hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S) may act as antioxidant molecules, the aim of this research was to evaluate the antioxidant effects of HYA and C4S treatment in a rat model of liver fibrosis. The effect on tissue inhibitors of metalloproteinases (TIMPs) was also studied. Liver fibrosis was induced in rats by eight intraperitoneal injections of CCl4, twice a week for 6 weeks. HYA or C4S alone (25 mg/kg) or HYA and C4S in combination (12.5 + 12.5 mg/kg) were administered daily by the same route during the 6 weeks. At the end of the 6-week treatment period (24 h after the last dose of GAGs), the following parameters were evaluated: (1) serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, as index of hepatic cell disruption; (2) hepatic conjugated dienes (CD), as index of lipid peroxidation; (3) hepatic TIMPs activity and expression; (4) hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as index of endogenous defences; (5) hepatic hydroxyproline, as index of collagen deposition. CCl4-induced liver fibrosis enhanced lipid peroxidation and TIMPs activation, increased ALT and AST, depleted antioxidants SOD and GPx, and caused collagen deposition in liver tissue. Treatment with GAGs, especially when in combination, successfully reduced ALT and AST rise, lipid peroxidation by evaluating conjugated dienes, TIMPs activation and mRNA expression, partially restored SOD and GPx activities, and limited collagen deposition in the hepatic tissue. The data obtained showed that these molecules were able to limit hepatic injury induced by chronic CCl4 intoxication and especially limited liver fibrosis. They also confirm that HYA and C4S may exert antioxidant mechanism, while reduction of TIMPs expression suggests that GAGs may influence MMPs and TIMPs imbalance in liver fibrosis.     

Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer

The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure of MYC-containing dmin/hsr amplicons harboring sequences from several different chromosomes in seven tumor cell lines, and characterized an unprecedented number of hsr insertion sites. Local chromosome shattering involving a single-step catastrophic event (chromothripsis) was recently proposed to explain clustered chromosomal rearrangements and genomic amplifications in cancer. Our bioinformatics analyses based on the listed criteria to define chromothripsis led us to exclude it as the driving force underlying amplicon genesis in our samples. Instead, the finding of coexisting heterogeneous amplicons, differing in their complexity and chromosome content, in cell lines derived from the same tumor indicated the occurrence of a multi-step evolutionary process in the genesis of dmin/hsr. Our integrated approach allowed us to gather a complete view of the complex chromosome rearrangements occurring within MYC amplicons, suggesting that more than one model may be invoked to explain the origin of dmin/hsr in cancer. Finally, we identified PVT1 as a target of fusion events, confirming its role as breakpoint hotspot in MYC amplification.     

Productivity and Temperature as Drivers of Seasonal and Spatial Variations of Dissolved Methane in the Southern Bight of the North Sea

Dissolved CH₄ concentrations in the Belgian coastal zone (North Sea) ranged between 670 nmol l^?1 nearshore and 4 nmol l^?1 offshore. Spatial variations of CH₄ were related to sediment organic matter (OM) content and gassy sediments. In nearshore stations with fine sand or muddy sediments, the CH₄ seasonal cycle followed water temperature, suggesting methanogenesis control by temperature in these OM-rich sediments. In offshore stations with permeable sediments, the CH₄ seasonal cycle showed a yearly peak following the chlorophyll-a spring peak, suggesting that in these OM-poor sediments, methanogenesis depended on freshly produced OM delivery. This does not exclude the possibility that some CH₄ might originate from dimethylsulfide (DMS) or dimethylsulfoniopropionate (DMSP) or methylphosphonate transformations in the most offshore stations. Yet, the average seasonal CH₄ cycle was unrelated to those of DMS(P), very abundant during the Phaeocystis bloom. The annual average CH₄ emission was 126 mmol m^?2 y^?1 in the most nearshore stations (~4 km from the coast) and 28 mmol m^?2 y^?1 in the most offshore stations (~23 km from the coast), 1260–280 times higher than the open ocean average value (0.1 mmol m^?2 y^?1). The strong control of CH₄ by sediment OM content and by temperature suggests that marine coastal CH₄ emissions, in particular in shallow areas, should respond to future eutrophication and warming of climate. This is supported by the comparison of CH₄ concentrations at five stations obtained in March 1990 and 2016, showing a decreasing trend consistent with alleviation of eutrophication in the area.     

Alta prevalencia de obesidad en una población laboral en España

Background and objectivesTo report the prevalence of obesity in a Spanish working population and its changes in recent years.Material and methodsData were collected from routine medical examinations performed on workers by a national mutual insurance society for occupational accidents and diseases (Ibermutuamur). A structured questionnaire was completed and physical examinations were performed. Overweight was defined as BMI ranging from 25 and 29.9, obesity as BMI of 30-39.9, and morbid obesity as BMI ≥ 40 kg/m².ResultsData from 1,336,055 medical examinations performed from May 2004 to November 2007 were collected. Prevalence rates in the population examined in 2004 (n = 230,684; 73% males; average age, 36.4 years) were: morbid obesity, 0.5% (0.6% males, 0.5% females); obesity, 14.5% (17.0% males, 7.7% females); overweight, 38.4% (44.8% males, 21.3% females). Prevalence rates of obesity and overweight were higher in blue-collar workers (16.4% and 40.5% respectively) as compared to white-collar workers (10.9% and 34.4% respectively). There was a progressive increase in prevalence of obesity during the 4-year study (2004-2007) in both males (17.0%, 17.6%, 17.9%, 18.2%) and females (7.6%, 8.0%, 8.4%, 8.7%).ConclusionsPrevalence of obesity and overweight in the Spanish working population is high, especially in male blue-collar workers, and is increasing. There is a need to promote early prevention programs and specific treatments for obesity.     

Topological Progression in Proliferating Epithelia Is Driven by a Unique Variation in Polygon Distribution

Morphogenesis is consequence of lots of small coordinated variations that occur during development. In proliferating stages, tissue growth is coupled to changes in shape and organization. A number of studies have analyzed the topological properties of proliferating epithelia using the Drosophila wing disc as a model. These works are based in the existence of a fixed distribution of these epithelial cells according to their number of sides. Cell division, cell rearrangements or a combination of both mechanisms have been proposed to be responsible for this polygonal assembling. Here, we have used different system biology methods to compare images from two close proliferative stages that present high morphological similarity. This approach enables us to search for traces of epithelial organization. First, we show that geometrical and network characteristics of individual cells are mainly dependent on their number of sides. Second, we find a significant divergence between the distribution of polygons in epithelia from mid-third instar larva versus early prepupa. We show that this alteration propagates into changes in epithelial organization. Remarkably, only the variation in polygon distribution driven by morphogenesis leads to progression in epithelial organization. In addition, we identify the relevant features that characterize these rearrangements. Our results reveal signs of epithelial homogenization during the growing phase, before the planar cell polarity pathway leads to the hexagonal packing of the epithelium during pupal stages.     

Effects of the administration of cadmium and zinc on the concentration of zinc in the thymus of rats

The zinc content of thymus glands of male Wistar rats has been determined during five weeks of treatment with ZnCl₂ and CdCl₂, and compared with a group of control rats. THymus gland extracts were chromatographed on columns of Sephadex G-75 and the zinc content of the one hundred fractions obtained were determined by atomic absorption spectrophotometry. The rats treated with ZnCl₂ showed an increase in the thymus concentration of zinc bound to high and low molecular weight proteins. The rats treated with CdCl₂ showed an increase in zinc concentration, as opposed to the control group, during the first three weeks of treatment, and thereafter show a toxic effect of cadmium on the gland, with ulterior regression of the latter, and a decrease in the concentration of zinc.     

OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA FROM LIVERS SHOWING CLOUDY SWELLING

Using succinate and α-ketoglutarate as substrates, oxidative phosphorylation has been measured in mitochondria isolated from livers showing cloudy swelling. This cellular change was obtained by injecting rats with S. typhi murium toxin and guinea pigs with diphtheria toxin. It has been found that phosphorylation associated with the oxidation of either of these substrates was partially inhibited in mitochondria from livers showing cloudy swelling, while the oxygen consumption was unchanged. Thus, the P:O ratios for both succinate and α-ketoglutarate were lower in mitochondria from treated animals than they were in normal mitochondria. Dephosphorylation of ATP was not significantly modified in mitochondria from livers showing cloudy swelling as compared with normal controls. No dephosphorylation of AMP and G-6-P was observed either in normal mitochondria or in mitochondria from treated animals.