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Usage of injectable dermal fillers applied for aesthetic purposes has extensively increased over the years. As such, the number of related adverse reactions has increased, including patients showing severe complications such as product migration, topical swelling and inflammatory reactions of the skin. In order to understand the underlying molecular events of these adverse reactions we performed a genome-wide gene expression study on the multi-cell type human Phenion® Full-Thickness Skin Model exposed to five experimental hyaluronic acid (HA) preparations with increasing cross-linking degree, four commercial fillers from Perfectha®, and non-resorbable filler Bio-Alcamid®. In addition, we evaluated whether cross-linking degree or particle size of the HA-based fillers could be associated with the occurrence of adverse effects. In all cases, exposure to different HA fillers resulted in a clearly elevated gene expression of cytokines and chemokines related to acute inflammation as part of the foreign body response. Furthermore, for one experimental filler genes of OXPHOS complexes I-V were significantly down-regulated (adjusted p-value < 0.05), resulting in mitochondrial dysfunction which can be linked to over-expression of pro-inflammatory cytokines TNFα and IL-1β and chemokine CCL2. Our hypothesis that cross-linking degree or particle size of the HA-based fillers is related to the biological responses induced by these fillers could only partially be confirmed for particle size. In conclusion, our innovative approach resulted in gene expression changes from a human 3D skin model exposed to dermal fillers that mechanistically substantiate aforementioned adverse reactions, and thereby adds to the weight of evidence that these fillers may induce inflammatory and fibrotic responses.

The high mortality in men with metastatic prostate cancer (PC) establishes the need for diagnostic optimization by new biomarkers. Mindful of the effect of real microgravity on metabolic pathways of carcinogenesis, we attended a parabolic flight (PF) mission to perform an experiment with the PC cell line PC-3, and submitted the resulting RNA to next generation sequencing (NGS) and quantitative real-time PCR (qPCR). After the first parabola, alterations of the F-actin cytoskeleton-like stress fibers and pseudopodia are visible. Moreover, numerous significant transcriptional changes are evident. We were able to identify a network of relevant PC cytokines and chemokines showing differential expression due to gravitational changes, particularly during the early flight phases. Together with differentially expressed regulatory lncRNAs and micro RNAs, we present a portfolio of 298 potential biomarkers. Via qPCR we identified IL6 and PIK3CB to be sensitive to vibration effects and hypergravity, respectively. Per NGS we detected five upregulated cytokines (CCL2, CXCL1, IL6, CXCL2, CCL20), one zink finger protein (TNFAIP3) and one glycoprotein (ICAM1) related to c-REL signaling and thus relevant for carcinogenesis as well as inflammatory aspects. We found regulated miR-221 and the co-localized lncRNA MIR222HG induced by PF maneuvers. miR-221 is related to the PC-3 growth rate and MIR222HG is a known risk factor for glioma susceptibility. These findings in real microgravity may further improve our understanding of PC and contribute to the development of new diagnostic tools.