Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review

Background: Fascioliasis has been sporadically associated with chronic liver disease on previous studies. In order to describe the current evidence, we carried out a systematic review to assess the association between fascioliasis with liver fibrosis, cirrhosis and cancer. Methodology and Principal Findings: A systematic search of electronic databases (PubMed, LILACS, Scopus, Embase, Cochrane, and Scielo) was conducted from June to July 2015 and yielded 1, 557 published studies. Among 21 studies that met inclusion and exclusion criteria, 12 studies explored the association of F. hepatica with liver fibrosis, 4 with liver cirrhosis, and 5 with cancer. Globally these studies suggested the ability of F. hepatica to promote liver fibrosis and cirrhosis. The role of F. hepatica in cancer is unknown. Given the heterogeneity of the studies, a meta-analysis could not be performed. Conclusions: Future high-quality studies are needed to determine the role of F. hepatica on the development of liver fibrosis, liver cirrhosis, and cancer in humans

In silico prediction of secretory proteins of Opisthorchis viverrini, Clonorchis sinensis and Fasciola hepatica that target the host cell nucleus

Liver flukes Fasciola hepatica, Opisthorchis viverrini and Clonorchis sinensis are causing agents of liver and hepatobiliary diseases. A remarkable difference between such worms is the fact that O. viverrini and C. sinensis are carcinogenic organisms whereas F. hepatica is not carcinogenic. The release of secretory factors by carcinogenic flukes seems to contribute to cancer development however if some of these target the host cell nuclei is unknown. We investigated the existence of O. viverrini and C. sinensis secretory proteins that target the nucleus of host cells and compared these with the corresponding proteins predicted in F. hepatica. Here we applied an algorithm composed by in silico approaches that screened and analyzed the potential genes predicted from genomes of liver flukes. We found 31 and 22 secretory proteins that target the nucleus of host cells in O. viverrini and C. sinensis, respectively, and that have no homologs in F. hepatica. These polypeptides have enriched the transcription initiation process and nucleic acid binding in O. viverrini and C. sinensis, respectively. In addition, other 11 secretory proteins of O. viverrini and C. sinensis, that target the nucleus of host cells, had F. hepatica homologs, have enriched RNA processing function. In conclusion, O. viverrini and C. sinensis have 31 and 22 genes, respectively, that may be involved in their carcinogenic action through a direct targeting on the host cell nuclei. © 2021 The Author(s

Screening the Pathogen Box for Identification of New Chemical Agents with Anti-Fasciola hepatica Activity

Fascioliasis is an infectious parasitic disease distributed globally and caused by the liver fluke Fasciola hepatica or F. gigantica. This neglected tropical disease affects both animals and humans, and it represents a latent public health problem due to the significant economic losses related to its effects on animal husbandry. For decades, triclabendazole has been the unique anti-Fasciola drug that can effectively treat this disease. However, triclabendazole resistance in fascioliasis has more recently been reported around the world, and thus, the discovery of novel drugs is an urgent need. The aim of this study was to investigate the fasciocidal properties of 400 compounds contained in the Pathogen Box. The first stage of the screening was carried out by measuring the fasciocidal activity on metacercariae at a concentration of 33 mu M each compound (the standard dose). Subsequently, the activities of the most active compounds (n = 33) at their 50% inhibitory concentration (IC50) values against metacercariae were assayed, and the results showed that 13 compounds had IC(50)s of 50%. Four hit compounds were selected on the basis of their predicted nontoxic properties, and the IC50 values obtained for adult worms were <10 mu M; thus, these compounds represented the best fasciocidal compounds tested here. A cytotoxicity assay on four types of cell lines demonstrated that three compounds were nontoxic at their most active concentration. In conclusion, three hit compounds identified in this proof-of-concept study are potential candidates in the discovery of new fasciocidal drugs. Further studies are warranted

Enhanced expression of the voltage-dependent anion channel 1 (VDAC1) in Alzheimer's disease transgenic mice: an insight into the pathogenic effects of amyloid-β

The mitochondrial voltage-dependent anion channel 1 (VDAC1) is involved in the release of apoptotic proteins with possible relevance in Alzheimer's disease (AD) neuropathology. Through proteomic analysis followed by Western blotting and immunohistochemical techniques, we have found that VDAC1 is overexpressed in the hippocampus from amyloidogenic AD transgenic mice models. VDAC1 was also overexpressed in postmortem brain tissue from AD patients at an advanced stage of the disease. Interestingly, amyloid-β (Aβ) soluble oligomers were able to induce upregulation of VDAC1 in a human neuroblastoma cell line, further supporting a correlation between Aβ levels and VDAC1 expression. In hippocampal extracts from transgenic mice, a significant increase was observed in the levels of VDAC1 phosphorylated at an epitope that is susceptible to phosphorylation by glycogen synthase kinase-3β, whose activity was also increased. The levels of hexokinase I (HXKI), which interacts with VDAC1 and affects its function, were decreased in mitochondrial samples from AD models. Since phospho-VDAC and reduced HXKI levels favors a VDAC1 conformational state more prone to the release proapoptotic factors, regulation of the function of this channel may be a promising therapeutic approach to combat AD

Treatment of obesity in children and adolescents. How nutrition can work?

Overweight appears when persistent positive energy imbalances occur for long periods of time. Knowledge of dietary risk factors during childhood and adolescence is needed in order to design preventive measures against the increase in the prevalence of obesity and its consequences but is, however, largely missing. Longitudinal studies in children have not found clear causal associations between energy intake or diet composition and overweight development. Research has been ongoing to develop effective intervention studies for obese children but it is not clear which intervention is the most effective in assisting overweight/obese children to improve body composition without affecting growth rates. The objective of this article is to review the available knowledge on dietary risk factors for the development of childhood obesity, to discuss different dietary treatment strategies, and to propose an evidence-based approach to treat obese adolescents

Mediterranean diet, diet quality, and bone mineral content in adolescents: the HELENA study

Summary: Dietary scores, rather than individual nutrients, allow exploring associations between overall diet and bone health. The aim of the present study was to assess the associations between the Mediterranean Diet Score for Adolescents (MDS-A) and the Diet Quality Index for Adolescents (DQI-A) and bone mineral content (BMC) among Spanish adolescents. Our results do not support an association between dietary scores or indices and BMC in adolescents. Introduction: To assess the associations between the MDS-A and a DQI-A with the BMC measured with dual-energy X-ray absorptiometry. Methods: The MDS-A and the DQI-A were calculated in 179 Spanish adolescents, based on two 24-h dietary recalls from the HELENA cross-sectional study. The associations between the diet scores and the BMC outcomes [total body less head (TBLH), femoral neck (FN), lumbar spine (LS), and hip] were analyzed using logistic regression models adjusting for several confounders. Results: Four hundred ninety-two models were included and only fruits and nuts and cereal and roots were found to provide significant ORs with regard to BMC. The risk of having low BMC reduced by 32% (OR 0.684; CI 0.473–0.988) for FN when following the ideal MDS-A, but this association lost significance when adjusting for lean mass and physical activity. For every 1-point increase in the cereal and root and the fruit and nut components, the risk of having low FN diminished by 56% (OR 0.442; CI 0.216–0.901) and by 67% (OR 0.332; CI 0.146–0.755), respectively. Conclusion: An overall dietary score or index is not associated with BMC in our adolescent Spanish sample

Error correction in short time steps during the application of quantum gates

We propose a method for applying the quantum error-correction method for errors that occur during quantum gates. Using a perturbation treatment of the noise that allows us to separate it from the ideal evolution of the quantum gate, we demonstrate that in certain cases it is necessary to divide the quantum gate in short time steps intercalated by correction procedures. A prescription of how these gates can be constructed is provided, as well as a proof that, even for the cases when the division of the quantum gate in short time steps is not necessary, this method may be advantageous for reducing the total duration of the computation

Correlates of ideal cardiovascular health in European adolescents: The HELENA study

Background and aims: The ideal cardiovascular health (iCVH) construct consists of 4 health behaviors (smoking status, body mass index, physical activity and diet) and 3 health factors (total cholesterol, blood pressure and fasting glucose). A greater number of iCVH components in adolescence are related to better cardiovascular health, but little is known about the correlates of iCVH in adolescents. Thus, the aim of the study was to examine correlates of iCVH in European adolescents. Methods and results: The study comprised 637 European adolescents with complete iCVH data. Participants were part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional, multicenter study conducted in 9 different European countries. Correlates investigated were sex and age, family affluence scale, maternal education, geographic location, sleep time, television viewing, duration of pregnancy, birth weight and breastfeeding. Younger adolescents, those whose mothers had medium/high education or those whowatched television less than 2 h per day had a greater number of iCVH components compared to those who were older, had a mother with low education or watched television 2 h or more daily (P <= 0.01). Conclusion: Since in our study older adolescents had worse iCVH than younger adolescents, early promotion of cardiovascular health may be important. Future studies mayalso investigate the usefulness of limiting television viewing to promote iCVH. Finally, since adolescents of mothers with low education had poorer iCVH, it may be of special interest to tailor public health promotion to adolescents from families with low socioeconomic status

Il6 gene promoter polymorphism (-174G/C) influences the association between fat mass and cardiovascular risk factors

During the last decades, the prevalence of obesity has increased rapidly among young people. A polymorphism in the promoter region of the IL6 gene (-174G/C), has been previously reported to be involved in obesity and metabolic syndrome development. Therefore, the aim of the study was to examine whether the IL6 -174G/C polymorphism influence the association of body fat with low-grade inflammatory markers and blood lipids and lipoproteins in Spanish adolescents. 504 Spanish adolescents participating in the AVENA study were genotyped for the -174G/C polymorphism of the IL6 gene. Anthropometric and body composition measurements were taken and blood samples were collected for plasma molecules determinations. No differences between genotypes were observed in anthropometric values, body composition measurements and plasma markers concentration. Physical activity level differ between genotypes with subjects carrying the C allele of the polymorphism being significantly (p<0.05) more active than GG subjects. The association between body fat mass and plasma glucose was influenced by the -174G/C polymorphism of the IL6 gene. Subjects carrying the C allele of the mutation seem to have higher values of lipoprotein (a) and C-reactive protein as their percentage of body fat mass increase. Our results suggest that this promoter polymorphism influences the association between adiposity and some plasma markers

Lifestyle patterns and endocrine, metabolic, and immunological biomarkers in European adolescents: The HELENA study

Objective: To evaluate the association of lifestyle patterns related to physical activity (PA), sedentariness, and sleep with endocrine, metabolic, and immunological health biomarkers in European adolescents. Methods: The present cross-sectional study comprised 3528 adolescents (1845 girls) (12.5-17.5 years) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Study. Cluster analysis was performed by including body composition, PA by accelerometry, self-reported sedentary behaviors, and sleep duration. We also measured endocrine, metabolic, and immunological biomarkers. Results: Three-cluster solutions were identified: (a) light-PA time, moderate-vigorous-PA time and sedentary time, (b) light-PA time, moderate-vigorous-PA time, sedentary time and sleep time, (c) light-PA time, moderate-vigorous-PA time, sedentary time and body composition. In addition, each cluster solution was defined as: “healthy, ” “medium healthy, ” and “unhealthy” according to the presented rating. Analysis of variance showed that overall the healthiest groups from the three clusters analyzed presented a better metabolic profile. A decision tree analysis showed that leptin had a strong association with cluster 3 in both boys and girls, high-density lipoprotein cholesterol had the strongest association with clusters 1 and 3 in boys. Cortisol had the strongest association with cluster 1. HOMA index (homeostatic model assessment) and C3 showed a strong association with cluster 3 in girls. Conclusions: Our results support the existence of different interactions between metabolic health and lifestyle patterns related to PA, sedentariness, and sleep, with some gender-specific findings. These results highlight the importance to consider multiple lifestyle-related health factors in the assessment of adolescents'' health to plan favorable strategies