On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis.

Recent advances in the development of human-based in vitro models offer new tools for drug screening and mechanistic investigations of new therapeutic agents. However, there is a lack of evidence that disease models respond favourably to potential drug candidates. Atopic dermatitis (AD) is a very common disease associated with an altered skin barrier and chronic inflammation. Here, we demonstrate that the AD-like features of a reconstructed human epidermis (RHE) model treated with Th2 cytokines are reversed in the presence of molecules known to have a beneficial effect on damaged skin as a result of modulating various signalling cascades including the Liver X Receptors and JAK/STAT pathways. This work shows that standardized and reproducible RHE are relevant models for therapeutic research assessing new drug candidates aiming to restore epidermal integrity in an inflammatory environment.

Feelings of shame and guilt are associated with distinct neural activation in youth.

Shame and guilt are moral emotions that play an important role in social functioning. There is limited knowledge about the neural underpinnings of these emotions, particularly in young people. In the current study, 36 healthy females (mean age 18.8 ± 1.9 years) underwent functional Magnetic Resonance Imaging, during which they reflected on their decisions about social moral dilemmas, and subsequently received negative or positive peer feedback. Ratings of shame and guilt were used as parametric modulators of brain activity. Shame was associated with decreased activity in the superior temporal sulcus and precentral gyrus during reflection. Guilt was associated with decreased activity in the precuneus during positive feedback, and in the hippocampus and supramarginal gyrus during negative feedback. Results suggest that shame and guilt are associated with activity in brain regions involved in social cognition and emotion regulation; however, they have distinct underlying neural circuitry that may be differentiated based on social evaluation.

Screening of senescence-associated genes with specific DNA array reveals the role of IGFBP-3 in premature senescence of human diploid fibroblasts.

Repeated exposures to sublethal concentrations of tert-butylhydroperoxide and ethanol trigger premature senescence of WI-38 human diploid fibroblasts. We found 16 replicative senescence-related genes with similar alterations in expression level in replicative senescence and two models of stress-induced premature senescence. Among these genes was IGFBP-3. Using a siRNA approach, we showed that IGFBP-3 regulates the appearance of several biomarkers of senescence after repeated exposures of WI-38 fibroblasts to tert-butylhydroperoxide and ethanol.

Feelings of shame, embarrassment and guilt and their neural correlates: A systematic review.

This systematic review aimed to provide a comprehensive summary of the current literature on the neurobiological underpinnings of the experience of the negative moral emotions: shame, embarrassment and guilt. PsycINFO, PubMed and MEDLINE were used to identify existing studies. Twenty-one functional and structural magnetic resonance imaging and positron emission tomography studies were reviewed. Although studies differed considerably in methodology, their findings highlight both shared and distinct patterns of brain structure/function associated with these emotions. Shame was more likely to be associated with activity in the dorsolateral prefrontal cortex, posterior cingulate cortex and sensorimotor cortex; embarrassment was more likely to be associated with activity in the ventrolateral prefrontal cortex and amygdala; guilt was more likely to be associated with activity in ventral anterior cingulate cortex, posterior temporal regions and the precuneus. Although results point to some common and some distinct neural underpinnings of these emotions, further research is required to replicate findings.

Neurodevelopmental correlates of proneness to guilt and shame in adolescence and early adulthood.

Investigating how brain development during adolescence and early adulthood underlies guilt- and shame-proneness may be important for understanding risk processes for mental disorders. The aim of this study was to investigate the neurodevelopmental correlates of interpersonal guilt- and shame-proneness in healthy adolescents and young adults using structural magnetic resonance imaging (sMRI). Sixty participants (age range: 15-25) completed sMRI and self-report measures of interpersonal guilt- and shame-proneness. Independent of interpersonal guilt, higher levels of shame-proneness were associated with thinner posterior cingulate cortex (PCC) thickness and smaller amygdala volume. Higher levels of shame-proneness were also associated with attenuated age-related reductions in thickness of lateral orbitofrontal cortex (lOFC). Our findings highlight the complexities in understanding brain-behavior relationships during the adolescent/young adult period. Results were consistent with growing evidence that accelerated cortical thinning during adolescence may be associated with superior socioemotional functioning. Further research is required to understand the implications of these findings for mental disorders characterized by higher levels of guilt and shame.

Comparison of replicative senescence and stress-induced premature senescence combining differential display and low-density DNA arrays.

Human diploid fibroblasts (HDFs) exposed to subcytotoxic stress display many features of senescence. Using differential display RT-PCR, gene expression of HDFs in premature senescence induced by tert-butylhydroperoxide or ethanol and in replicative senescence was compared to gene expression of HDFs at early cumulative population doublings. Thirty genes of known function were identified from the 265 differentially displayed cDNA fragments. A customized low-density array allowed to confirm the relative level of the corresponding 30 transcripts. We found differential expression of genes coding for proteins implicated namely in growth arrest (PTEN, IGFBP-3, LRP-1 and CAV1), senescent morphogenesis (TGF-beta1 and LOXL2) and iron metabolism (TFR and FTL).