Biology subjects

Tanaskovic, N.

Publications and source records attributed to Tanaskovic, N..

3 recordsLinked to original sources

bioRxiv2024

Lactobacillus paracasei CNCM I-5220-derived postbiotic counteracts skin inflammation and protects skin barrier integrity

IntroductionSkin inflammation and damage of skin barrier integrity contribute to the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis. Nowadays, there is a growing interest in alternative and complementary strategies to counteract skin inflammation and treat dermatologic conditions. ObjectivesPostbiotics, metabolites released during bacterial fermentation, exert anti-inflammatory proprieties and contribute to the maintenance of epithelial barrier integrity. Therefore, we investigated the effect of LP-PBL, a novel Lactobacillus paracasei CNCM I-5220-derived postbiotic, in controlling skin inflammation and protecting the skin barrier. MethodsWe performed RNA-sequencing on Poly(I:C)-stimulated keratinocytes and investigated LP-PBL efficacy in regulating pro-inflammatory cytokine release. The production of most relevant cytokines was demonstrated by ELISA. Then, we tested postbiotic lenitive efficacy on healthy volunteers irritated skin. We compared the effect of a postbiotic-containing cream formulation versus placebo on sodium lauryl sulphate treated skin. ResultsWe demonstrate that LP-PBL has anti-inflammatory activity by modulating Poly(I:C)-dependent inflammatory pathways and pro-inflammatory cytokine release in keratinocytes. The postbiotic inhibited the upregulation of interleukin (IL)-23A, which is overexpressed in psoriatic skin, and of IL-33 and thymic stromal lymphopoietin (TSLP) that are upregulated in atopic dermatitis. Moreover, it increased filaggrin and zonula occludens (ZO)-1 expression in Poly(I:C)-stimulated keratinocytes, suggesting beneficial effects on inflamed and damaged skin. Consistently, a clinical test on healthy volunteers showed that topic LP-PBL treatment significantly reduced skin redness upon sodium lauryl sulphate challenge compared to placebo, leading to a rapid recovery of the irritated skin. ConclusionOverall, we demonstrated the protective role of LP-PBL on the skin, both in vitro and in the clinical test, suggesting that postbiotic topical application could represent an innovative and promising strategy to counteract skin inflammation and preserve skin barrier integrity.

microbiology↗

bioRxiv2021

Polycomb Group Ring Finger Protein 6 suppresses Myc-induced lymphomagenesis

Max is an obligate dimerization partner for the Myc transcription factors and for several repressors, such as Mnt, Mxd1-4 and Mga, collectively thought to antagonize Myc function in transcription and oncogenesis. Mga, in particular, is part of the variant Polycomb group repressive complex PRC1.6. Here, we show that ablation of the distinct PRC1.6 subunit Pcgf6 - but not Mga - accelerates Myc-induced lymphomagenesis in E{micro}-myc transgenic mice. Unexpectedly, however, Pcgf6 loss shows no significant impact on transcriptional profiles, in neither pre-tumoral B-cells, nor lymphomas. Altogether, these data unravel an unforeseen, Mga- and PRC1.6-independent tumor suppressor activity of Pcgf6.

cancer biology↗

bioRxiv2019

Cooperation between MYC and β-catenin in liver tumorigenesis requires Yap/Taz

Background & AimsActivation of MYC and CTNNB1 (encoding {beta}-catenin) can co-occur in liver cancer, but how these oncogenes cooperate in tumorigenesis remains unclear.\n\nApproach & ResultsWe generated a mouse model allowing conditional activation of MYC and WNT/{beta}-catenin signaling (through either {beta}-catenin activation or Apc loss) upon expression of CRE recombinase in the liver, and monitored their effects on hepatocyte proliferation, apoptosis, gene expression profiles and tumorigenesis. Conditional activation of WNT/{beta}-catenin signaling strongly accelerated MYC-driven carcinogenesis in the mouse liver. Both pathways also cooperated in promoting cellular transformation in vitro, demonstrating their cell-autonomous action. Short-term induction of MYC and {beta}-catenin in hepatocytes followed by RNA-seq profiling allowed the identification of a \"Myc/{beta}-catenin signature\", composed of a discrete set of Myc-activated genes whose expression increased in presence of active {beta}-catenin. Notably this signature enriched for targets of Yap and Taz, two transcriptional co-activators known to be activated by WNT/{beta}-catenin signaling, and to cooperate with MYC in mitogenic activation and liver transformation. Consistent with these regulatory connections, Yap/Taz accumulated upon Myc/{beta}-catenin activation and were required not only for the ensuing proliferative response, but also for tumor cell growth and survival. Finally, the Myc/{beta}-catenin signature was enriched in a subset of human hepatocellular carcinomas characterized by comparatively poor prognosis.\n\nConclusionsYap and Taz mediate the cooperative action of Myc and {beta}-catenin in liver tumorigenesis. This warrants efforts toward therapeutic targeting of Yap/Taz in aggressive liver tumors marked by elevated Myc/{beta}-catenin activity.

cancer biology↗