Inhibition of the liver expression of arylalkylamine N-acetyltransferase increases the expression of angiogenic factors in cholangiocytes

Background and aims

Reduction of biliary serotonin N-acetyltransferase (AANAT) expression and melatonin administration/secretion in cholangiocytes increases biliary proliferation and the expression of SR, CFTR and Cl^–/HCO₃^– AE2. The balance between biliary proliferation/damage is regulated by several autocrine neuroendocrine factors including vascular endothelial growth factor-A/C (VEGF-A/C). VEGFs are secreted by several epithelia, where they modulate cell growth by autocrine and paracrine mechanisms. No data exists regarding the effect of AANAT modulation on the expressions of VEGFs by cholangiocytes.

Methods

In this study, we evaluated the effect of local modulation of biliary AANAT expression on the cholangiocytes synthesis of VEGF-A/C.

Results

The decrease in AANAT expression and subsequent lower melatonin secretion by cholangiocytes was associated with increased expression of VEGF-A/C. Overexpression of AANAT in cholangiocyte lines decreased the expression of VEGF-A/C.

Conclusions

Modulation of melatonin synthesis may affect the expression of VEGF-A/C by cholangiocytes and may modulate the hepatic microvascularization through the regulation of VEGF-A/C expression regulating biliary functions.     

Shall we use non-verbal fluency in schizophrenia? – A pilot study

Over the last few years, numerous studies have attempted to explain fluency impairments in people with schizophrenia, leading to heterogeneous results. This could notably be due to the fact that fluency is often used in its verbal form where semantic dimensions are implied. In order to gain an in-depth understanding of fluency deficits, a non-verbal fluency task – the Five-Point Test (5PT) – was proposed to 24 patients with schizophrenia and to 24 healthy subjects categorized in terms of age, gender and schooling. The 5PT involves producing as many abstract figures as possible within 1 min by connecting points with straight lines. All subjects also completed the Frontal Assessment Battery (FAB) while those with schizophrenia were further assessed using the Positive and Negative Syndrome Scale (PANSS). Results show that the 5PT evaluation differentiates patients from healthy subjects with regard to the number of figures produced. Patients? results also suggest that the number of figures produced is linked to the “overall executive functioning” and to some inhibition components. Although this study is a first step in the non-verbal efficiency research field, we believe that experimental psychopathology could benefit from the investigations on non-verbal fluency.     

Family and Lifestyle Factors Mediate the Relationship between Socioeconomic Status and Fat Mass in Children and Adolescents

Socioeconomic status (SES) is strongly associated with childhood overweight. The underlying mechanism and the role of family and lifestyle factors as potential mediators of this relationship remain, however, unclear. Cross-sectional data of 4,772 girls and boys aged 5–16 years from the Kiel Obesity Prevention Study were considered in mediation analyses. Fat mass (FM) was assessed by bioelectrical impedance analysis and converted into a percent FM SD score (FM%-SDS). SES was defined by the parental educational level, classified as low, middle, or high. Characteristics of family and lifestyle factors were obtained via validated questionnaires and considered as mediators. In 3 different age groups, the product-of-coefficients method was used to examine age-specific mediator effects on the relationship between SES and FM%-SDS (c = total effects) and their ratio to total effects, adjusted for age, sex, puberty, and nationality. The prevalence of overweight was 6.9%. In all age groups, SES was inversely associated with FM%-SDS as follows: 5–7 years, c₁ = −0.11 (95% CI −0.19 to −0.03); 9–11 years, c₂ = −0.21 (95% CI −0.27 to −0.14); and 13–16 years, c₃ = −0.23 (95% CI −0.28 to −0.17). The relationship between SES and FM%-SDS was fully (5–7 and 9–11 years) and partly (13–16 years) mediated by similar and age-specific mediators, including parental BMI, parental smoking habits, media consumption, physical activity, and shared meals. Overall, these variables resulted in a total mediating effect of 77.8% (5–7 years), 82.4% (9–11 years), and 70.6% (13–16 years). Consistent for both sexes, the relationship between SES and FM%-SDS was therefore mediated by parental weight status, risk-related behavior within families, and children''s and adolescents'' lifestyle factors. Strategies for obesity prevention, which are predominantly targeted at socially disadvantaged groups, should therefore address the family environment and lifestyle factors.