Untersuchung zur Bedeutung von STAT3 in der kutanen Abwehr

Die Haut ist permanent einer Vielzahl von potentiell pathogenen Mikroorganismen ausgesetzt. Die Epithelzellen der Haut sind in der Lage Mikroorganismen zu erkennen und nachfolgend eine Verteidigungsreaktion durch die Expression von Abwehrmolekülen zu initiieren. Über die beteiligten Signaltransduktionswege, die zur mikroorganismeninduzierten Expression von Abwehrmolekülen führen, ist noch wenig bekannt. In dieser Arbeit wurde der Frage nachgegangen, in wieweit das Signaltransduktionsmolekül STAT3 die Expression von antimikrobiellen Peptiden (AMPs) und Zytokinen nach Stimulation von Keratinozyten mit Bakterien (Staphylococcus aureus) vermittelt. Eine Dysregulation des STAT3-Signalweges und eine daraus resultierende defekte epidermale Abwehr könnte zu einer erhöhten Infektanfälligkeit beitragen, so wie es in Patienten mit Mutationen im STAT3 Gen beschrieben wurde. Diese Patienten leiden unter dem so genannten Hyper-IgE-Syndrom (HIES) und haben neben Lungeninfektionen auch Infektionen der Haut, vor allem mit Staphylococcus aureus. In dieser Arbeit wurde genauer untersucht, inwieweit die STAT3 Mutation die Abwehrstrategien von Keratinozyten betrifft, um so die gestörte Abwehr der HIES-Patienten besser zu verstehen. Dazu wurde STAT3 mittels einer STAT3-siRNA und einem STAT3-Inhibitor in Keratinozyten und in Hautbiopsien herunterreguliert und die AMP- und Zytokinexpressionslevel mittels „real-time“-PCR analysiert. Es konnte gezeigt werden, dass mehrere AMPs (Psoriasin, hBD-3 und RNase 7) und IL-17C als wichtiges epidermales Zytokin durch die Stimulation mit Staphylococcus aureus induziert werden. Diese Induktion konnte durch die STAT3-Hemmung signifikant gemindert werden. Somit lässt sich schlussfolgern, dass die genannten Abwehrstoffe auch bei den HIES-Patienten weniger gebildet werden könnten. Dementsprechend liefert die hier vorliegende Arbeit Hinweise für eine Dysregulation des epidermalen Abwehrsystems bei diesen Patienten und trägt zum Verständnis des Zusammenhangs zwischen STAT3-Mutation und erhöhter kutaner Infektanfälligkeit bei

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions