Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women

OBJECTIVE: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. METHOD: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). RESULTS: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. CONCLUSION: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity

Cognitive, affective and feedback-based flexibility – disentangling shared and different aspects of psychological flexibility

The current study aims at disentangling shared and different aspects of psychological flexibility on a mechanistic level

Neural correlates of affective task switching and asymmetric affective task switching costs

The control of emotions is of potentially great clinical relevance. Accordingly, there has been increasing interest in understanding the cognitive mechanisms underlying the ability to switch efficiently between the processing of affective and non-affective information. Reports of asymmetrically increased switch costs when switching towards the more salient emotion task indicate specific demands in the flexible control of emotion. The neural mechanisms underlying affective task switching, however, are so far not fully understood. Using functional MRI (N=57), we observed that affective task switching was accompanied by increased activity in domain-general fronto-parietal control systems. BOLD activity in posterior medial frontal and anterolateral prefrontal cortex was directly related to affective switch costs, indicating that these regions play a particular role in individual differences in (affective) task switching ability. Asymmetric switch costs were associated with increased activity in right inferior frontal and dorsal anterior medial prefrontal cortex, two brain regions critical for response inhibition. This suggests that asymmetric switch costs might – to a great extent – reflect higher demands on inhibitory control of the dominant emotion task. These results contribute to a refined understanding of brain systems for the flexible control of emotions, and thereby identify valuable target systems for future clinical research

Cognitive, affective, and feedback-based flexibility – disentangling shared and different aspects of three facets of psychological flexibility

Cognitive flexibility – the ability to adjust one ́s behavior to changing environmental demands – is crucial for controlled behavior. However, the term ‘cognitive flexibility’ is used heterogeneously, and associations between cognitive flexibility and other facets of flexible behavior have only rarely been studied systematically. To resolve some of these conceptual uncertainties, we directly compared cognitive flexibility (cue-instructed switching between two affectively neutral tasks), affective flexibility (switching between a neutral and an affective task using emotional stimuli), and feedback-based flexibility (non-cued, feedback-dependent switching between two neutral tasks). Three experimental paradigms were established that share as many procedural features (in terms of stimuli and/or task rules) as possible and administered in a pre-registered study plan (N=100). Correlation analyses revealed significant associations between the efficiency of cognitive and affective task switching (response time switch costs). Feedback-based flexibility (measured as mean number of errors after rule reversals) did not correlate with task switching efficiency in the other paradigms, but selectively with the effectiveness of affective switching (error rate costs when switching from neutral to emotion task). While preregistered confirmatory factor analysis (CFA) provided no clear evidence for a shared factor underlying the efficiency of switching in all three domains of flexibility, an exploratory CFA suggested commonalities regarding switching effectiveness (accuracy-based switch costs). We propose shared mechanisms controlling the efficiency of cue-dependent task switching across domains, while the relationship to feedback-based flexibility may depend on mechanisms controlling switching effectiveness. Our results call for a more stringent conceptual differentiation between different variants of psychological flexibility

Individual differences in resilience to stress are associated with affective flexibility

Cognitive flexibility, the capacity to adjust behavior to changing situational demands, is frequently linked to resilience because of its important contribution to stress regulation. In this context, particularly affective flexibility, defined as the ability to flexibly attend and disengage from affective information, may play a significant role. However, there are so far only very few empirical investigations that directly explore the link between flexibility and resilience to stress. In the present study, the relationship of cognitive and affective flexibility and resilience was examined in 100 healthy participants. Resilience was measured with three self-report questionnaires, two defining resilience as a personality trait and one focusing on resilience as an outcome in the sense of stress coping abilities. Cognitive and affective flexibility were assessed in two experimental task switching paradigms with non-affective and affective materials and tasks, respectively. The cognitive flexibility paradigm additionally included measures of cognitive stability and dispositional cognitive flexibility. In the affective flexibility paradigm, we explicitly considered the affective valence of the stimuli before and during task switching. Response time switch costs in the affective flexibility paradigm were significantly correlated to all three self-report measures of resilience. Regarding the valence of the stimuli, the correlation with resilience was not specific to costs when switching from negative to positive information or vice versa. For cognitive (i.e., non-affective) flexibility, a significant correlation of response time switch costs was found with only one of the three resilience measures. A regression analysis including both affective and cognitive switch costs as predictors of resilience indicated that only affective, but not cognitive switch costs, explained unique variance components. Furthermore, the experimental measures of cognitive stability and dispositional cognitive flexibility did not correlate with resilience scores. These findings suggest that specifically the efficiency of flexibly switching between affective and non-affective information is related to resilience

Predicting individual differences in resilience by cognitive and affective flexibility

Resilience research aims at finding traits or predispositions that protect from developing mental disorders despite exposure to stress or adversity. One psychosocial factor that is frequently linked to resilience is psychological flexibility. So far, only one study has focused on the association of cognitive and affective flexibility and resilience. The current study aims at replicating and extending these findings. For this purpose, resilience and flexibility will be examined in a sample of 100 healthy subjects. To measure resilience, three self-report questionnaires will be applied: two that define resilience as a personality trait and one that focuses on resilience as an outcome in the sense of stress coping abilities. Cognitive and affective flexibility will be assessed as switch costs (increases in response times and error rates when switching between two tasks) in two experimental paradigms

Cognitive, affective, and feedback-based flexibility : disentangling shared and different aspects of three facets of psychological flexibility

Cognitive flexibility – the ability to adjust one’s behavior to changing environmental demands – is crucial for controlled behavior. However, the term ‘cognitive flexibility’ is used heterogeneously, and associations between cognitive flexibility and other facets of flexible behavior have only rarely been studied systematically. To resolve some of these conceptual uncertainties, we directly compared cognitive flexibility (cue-instructed switching between two affectively neutral tasks), affective flexibility (switching between a neutral and an affective task using emotional stimuli), and feedback-based flexibility (non-cued, feedback-dependent switching between two neutral tasks). Three experimental paradigms were established that share as many procedural features (in terms of stimuli and/or task rules) as possible and administered in a pre-registered study plan (N = 100). Correlation analyses revealed significant associations between the efficiency of cognitive and affective task switching (response time switch costs). Feedback-based flexibility (measured as mean number of errors after rule reversals) did not correlate with task switching efficiency in the other paradigms, but selectively with the effectiveness of affective switching (error rate costs when switching from neutral to emotion task). While preregistered confirmatory factor analysis (CFA) provided no clear evidence for a shared factor underlying the efficiency of switching in all three domains of flexibility, an exploratory CFA suggested commonalities regarding switching effectiveness (accuracy-based switch costs). We propose shared mechanisms controlling the efficiency of cue-dependent task switching across domains, while the relationship to feedback-based flexibility may depend on mechanisms controlling switching effectiveness. Our results call for a more stringent conceptual differentiation between different variants of psychological flexibility