Cytokine expression patterns in hospitalized children with Bordetella pertussis, Rhinovirus or co-infection

Mechanisms of interaction between Bordetella pertussis and other viral agents are yet to be fully explored. We studied the inflammatory cytokine expression patterns among children with both viral-bacterial infections. Nasopharyngeal aspirate (NPA) samples were taken from children, aged < 1 year, positive for Rhinovirus, Bordetella pertussis and for Rhinovirus and Bordetella pertussis. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Our results show that co-infections display a different inflammatory pattern compared to single infections, suggesting that a chronic inflammation caused by one of the two pathogens could be the trigger for exacerbation in co-infections

HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation

Background and aims: Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Methods: Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). Results: After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. Conclusions: Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy

Blood cell gene expression profiles: A narrative review of biomarkers and effects of low-dose ionizing radiation exposure

Ionizing radiation (IR) is a ubiquitous environmental agent whose effects on organisms are well known. This review pro-vides a summary about definitions and man-made low-dose ionizing radiation (LDIR) sources and dosimeters used in radiation protection. Moreover, the main purpose of this article was to overview the pro-oncogenic effects of LDIR, and to provide experimental evidence that reinforce the use of gene expression data as biomarkers of LDIR effects. Our review showed that basic studies on biological response to LDIR are considered priority. Further, understanding occupational exposure to LDIR may provide valuable information to organize the prevention and prevent from the onset of long-term health effects in radiation workers. Currently, the biodosimetry-based assessment in certain high-risk occupational groups may be performed by using peripheral blood cells as samples for testing and validation of biomarkers specificity and sensi-tivity. Most of the studies on this topic are aimed at establishing new biomarkers and approaches to biological dosimetry, for allowing non-invasive monitoring of long-term health effects of LDIR. Analysis on changes in gene-expression, which is an early specific biological response to LDIR, could provide rapid estimates of individual dose in occupational cohorts, improving the management of periodical medical examination in subjects exposed to LDIR sources

Pediatric Non-Alcoholic Fatty Liver Disease Is Affected by Genetic Variants Involved in Lifespan/Healthspan

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan-related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children. METHODS: We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin-6 [IL-6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD-related metabolic and liver features in 177 pediatric patients with biopsy-proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case-control analysis of SNP-SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features. RESULTS: Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL-6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP-SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024). CONCLUSION: In conclusion, here we demonstrated a synergic interaction between IL-6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD-associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD

Toll-like receptor 4: A starting point for proinflammatory signals in fatty liver disease

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Targeting FGF19 binding to its receptor system: A novel therapeutic approach for hepatocellular carcinoma

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Is obesity in childhood protective for breast cancer in young women?

Islami et al. (1) reported the proportion and the type of cancers that are referable to excess of body weight (EBW) in United States. The study revealed 37,670 cancer cases in men and 74,690 cancer cases in women 30 years or older in US from 2011 to 2015 that could be ascribed to high body mass index. Interestingly, Islami et al. (1), found that the amount of population attributable fraction (PAF) for EBW was higher in women than in men, paralleling the close association between high body mass index (BMI) and increased risk for several female-specific cancers, such as breast cancer. Data on breast cancer are in line with the findings of the Women’s Health Initiative Clinical Trial that reported an association of obesity with increased invasive breast cancer risk in postmenopausal women (2). However, in both of above mentioned studies the association between increased risk of breast cancer and EBW has been reported only for postmenopausal women, excluding from the analysis women younger than approximately 50 years. Postmenopausal women often exhibit high BMI, likely due to a decrease in basal metabolism, alteration of hormonal levels, and reduced physical activity with an increased risk of developing some types of cancer. Therefore, the promotion of healthy lifestyles through physical activity, education and food policies that point to reduce weight gain should be considered as preventive care in postmenopausal women. On the other hand, previous studies have reported that high BMI in children appears to decrease breast cancer risk in both premenopausal and postmenopausal years (3,4). These lines of evidence suggest that both the timing and duration of excessive weight gain might be key factors that influence breast cancer risk in adulthood. Therefore, the study by Islami et al. (1) could be well-implemented through future studies that retrieve weight history at different ages with the aim to establish how development of breast cancer is associated with the time-period of exposure to EBW. Moreover, further prospective cohort studies should be performed in women who have suffered obesity in childhood because their results might provide important clues to the pathogenesis and effective personalized management for breast cancer in the obese population

Low birth weight and catch-up-growth associated with metabolic syndrome: a ten-year systematic review

Objective: We conducted a systematic review in order to: i. summarize the relationship between low birth weight, catch-up-growth and the metabolic syndrome, from publications during the past 10 years; and ii. study the potential role of an alternative nurtritional approach to side effects of catch-up-growth. Methods: We reviewed all papers published in the past ten years assessing the possible association between low birth weight, cathch-up-growth and the occurrence of some components of the metabolic syndrome, including insulin resistance, type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease. Results: We found 57 studies which described the relationship between metabolic syndrome associated features and low birth weight and catch-up-growth. The majority of the studies in children, adolescents and adults born small for gestational age (SGA) suggested that insulin resistance could represent the prelude to other metabolic disorders. Conclusions: Both low birth weight and catch-up-growth seem to correlate with some aspects of a later metabolic syndrome