High Serum Cyclophilin C levels as a risk factor marker for Coronary Artery Disease

Cyclophilins (Cyps) are ubiquitous proteins that belong to the immunophilins family consistently associated with inflammatory and cardiovascular diseases. While levels of CypA have been extensively studied, less data are available for other Cyps. The purpose of this case-control study was to determine the relationship of Cyps (A, B, C and D) with coronary artery disease (CAD) and eight inflammation markers. Serum levels of Cyps, interleukins and metalloproteinases were measured in serum collected from 84 subjects. Participants were divided into two sub-groups based on CAD diagnosis: 40 CAD patients and 44 control volunteers. Serum levels of CypA, CypB and CypC, IL-1β and IL-6 were significantly higher in CAD patients. Bivariate correlation analysis revealed a significant positive correlation between Cyps and several blood and biochemical parameters. When the ability of Cyps levels for CAD diagnosis was evaluated, higher sensitivity and selectivity values were obtained with CypC (c-statistic 0.891, p < 0.001) indicating that it is a good marker of CAD disease, while less conclusive results were obtained with CypA (c-statistic 0.748, p < 0.001) and CypB (c-statistic 0.655, p < 0.014). In addition, significant correlations of traditional CAD risk factors and CypC were observed. In summary, high levels of CypC are a risk factor for CAD and therefore it can be proposed as a new biomarker for this disease.This work could not have been done without the invaluable collaboration of the staff at the Servicio Vixilancia da Saude from Universidad de Santiago de Compostela (Andrea Vidal Dopazo) and at the Cardiology Department, Hospital Universitario Lucus Augusti (Maria Jesús Basanta-Castro, Maria del Carmen Cabarcos Leal, Clara Jimenez-Serrano, Leonor Ortega- Fernández, Maria Jesus Palacios Pool, Sofía Seco-Aldegunde). The research leading to these results has received funding from the following FEDER cofunded-grants. From Conselleria de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830, ISCIII/PI16/01816 and RTC-2016-5507-2, ITC-20161072. From European Union POCTEP 0161-Nanoeaters -1-E-1, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018, and H2020 778069-EMERTOX. Sandra Gegunde was supported by a fellowship from FIDIS, Spain

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases

The insect, Galleria mellonella, is a compatible model for evaluating the toxicology of okadaic acid

The polyether toxin, okadaic acid, causes diarrhetic shellfish poisoning in humans. Despite extensive research into its cellular targets using rodent models, we know little about its putative effect(s) on innate immunity. We inoculated larvae of the greater waxmoth, Galleria mellonella, with physiologically relevant doses of okadaic acid by direct injection into the haemocoel (body cavity) and/or gavage (force-feeding). We monitored larval survival and employed a range of cellular and biochemical assays to assess the potential harmful effects of okadaic acid. Okadaic acid at concentrations >75 ng/larva (>242 µg/kg) led to significant reductions in larval survival (>65%) and circulating haemocyte (blood cell) numbers (>50%) within 24 h post-inoculation. In the haemolymph, okadaic acid reduced haemocyte viability and increased phenoloxidase activities. In the midgut, okadaic acid induced oxidative damage as determined by increases in superoxide dismutase activity and levels of malondialdehyde (i.e., lipid peroxidation). Our observations of insect larvae correspond broadly to data published using rodent models of shellfish poisoning toxidrome, including complementary LD50 values; 206–242 μg/kg in mice, ~239 μg/kg in G. mellonella. These data support the use of this insect as a surrogate model for the investigation of marine toxins, which offers distinct ethical and financial incentives

Effect of alkaloids isolated from Haliclona sp. against hydrogen peroxide-induced injury in SH-SY5Y human neuroblastoma cells

International audienceThe great biodiversity of the oceans makes the marine environment a rich source of new bioactive compounds. Particularly, marine sponges have provided several secondary metabolites with potential pharmaceutical applications. Sarains are diamide alkaloids isolated from the Mediterranean sponge Haliclona (Rhizoniera) sarai that have already showed antibacterial, insecticidal and anti-fouling activity. In this study, we examined for first time the neuroprotective effects of sarains 1, 2 and A against oxidative stress. With this purpose, sarains were tested in an in vitro oxidative stress model using human neuroblastoma SH-SY5Y cells. Compounds were co-incubated with hydrogen peroxide for 6 hours and protective effects were evaluated. Sarain A was the most promising compound, improving mitochondrial function and decreasing reactive oxygen species levels (ROS). In view of these results, the ability of sarain A to induce the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element pathway was determined. This compound enhanced Nrf2 translocation to the nucleus, which suggests that sarain A is acting as an indirect antioxidant.Oxidative stress produces mitochondrial dysfunction, which is related to neurodegenerative disorders as Alzheimer's, Parkinson's and Huntington diseases. Therefore, diminishing ROS release and improving antioxidant systems might be a potential therapeutic strategy against these illnesses. Indirect antioxidants, more than direct ones, are considered a promising tool to decrease oxidative stress because they can induce the expression of cytoprotective proteins and reduce mitochondrial dysfunction. Our results indicate that sarain A may be a candidate compound for further studies in neurodegenerative diseases

Dynamics of co-occurring Alexandrium minutum (Global Clade) and A. tamarense (West European) (Dinophyceae) during a summer bloom in Cork Harbour, Ireland (2006)

The dinoflagellate genus Alexandrium contains neurotoxin-producing species, which have adversely affected the aquaculture industry and fisheries worldwide. Seasonal toxic blooms of Alexandrium spp. occur on an annual basis in the North Channel area of Cork Harbour, Ireland, where resident populations of non-toxic A. tamarense (West European ribotype) and PSP toxin-producing A. minutum (Global Clade) co-occur. Field surveys were carried out throughout a bloom of Alexandrium spp. in the summer of 2006. Taxa-specific fluorescently labelled probes were used in a dual whole-cell fluorescent in situ hybridization (WC-FISH) assay for the simultaneous discrimination and quantification of A. minutum and A. tamarense in the water column. The bloom occurred following a weak spring tide in early June and Alexandrium cell concentrations exceeded 3×104 cells L-1. A. minutum dominated numerically over A. tamarense throughout the sampling period (74% on average). The maximum cell concentration was ∼3.3×105 cells L-1 at the peak of the bloom and was localized at the eastern end of the North Channel. The bloom collapse coincided with increasing tidal flushing and significantly changing meteorological conditions (wind speed increase, lesser irradiance), which led to a water temperature drop of ∼3 °C within a period of 7 days. GTX3 was the dominant PSP toxin variant and C-toxins were at times observed in samples. Assuming that A. minutum was the only microorganism synthesising PSP toxins, the internal toxin quota was on average 13.4 fmol cell-1, a value similar to that observed in laboratory experiments. Monitoring of toxic Alexandrium species in Ireland will require the use of molecular methods for reliable discrimination and quantification. © 2009 Elsevier Ltd. All rights reserved