Betula alba Bark Extract and Empetrum nigrum Fruit Juice, a Natural Alternative to Niacinamide for Skin Barrier Benefits.

The Scandinavian region is home to a unique biome with endemic plant species. The aim of this study was to explore this natural diversity and identify plant extracts providing positive skin barrier effects. Six plant extracts were identified as starting material. Following biochemical screening, two candidates outperformed the rest: Betula alba (BA) and Empetrum nigrum (EN). Quantitative PCR analysis showed that BA and EN upregulated barrier genes, when used individually and in combination. Betula alba increased AQP3 and OCLN protein expression, something niacinamide was incapable of. Additionally, the skin barrier was strengthened, evidenced by inhibition of KLK5 and hyaluronidase and showed strong antioxidant and anti-inflammatory activity through DPPH and COX2 inhibition, respectively. A first split-face clinical study was conducted using the combination of extracts versus placebo. There was a significantly better skin restructuring effect and corneocyte cohesion on the side treated with combined extracts. A second split-face clinical study assessed the combined extracts versus 3% niacinamide. Significant variations in skin hydration and TEWL were observed in favor of the extract treated side. In conclusion, we identified a natural alternative to niacinamide for improving skin barrier health, in Scandinavian plant extracts, which yield strong performance, but at a lower concentration.

A novel multifunctional skin care formulation with a unique blend of antipollution, brightening and antiaging active complexes.

BACKGROUND: High demand on anti-aging skin care encourage the improvement and development of more personalized formulations with additional benefits for general skin health and age associated skin signs. The skin aging physical and biological phenotypes manifest differently between diverse ethnic populations. A highly polluted environment can be viewed as an extrinsic factor accelerating the skin aging process. AIM: To develop a unique formula with active complexes, having multifunctional effects for anti-pollution, brightening and anti-aging/barrier strengthening purposes with confirmed activities in vitro and ex vivo skin models, suitable for polluted skin. METHODS: In vitro culture model with primary human skin cells, ex vivo studies with full-thickness human skin, melanocyte 3D coculture model, gene expression of epidermal and dermal genes, anti-glycation, proteasomal activity, melanin, and cytokine assays. RESULTS: In vitro and ex vivo studies clearly demonstrated that diglucosyl gallic acid (active A) and the formulation complex inhibited pollution mediated MMP1 protein, CYP1A1 gene expression, and IL-6 protein secretion, while caprylic/capric triglyceride, diacetyl boldine (active B) had anti-melanogenic effect in in vitro primary melanocyte monoculture and 3D spheroid model. Another active compound, acetyl dipeptide 1 cetyl ester (active D), significantly upregulated epidermal barrier genes (Aquaporin 3 [AQP3], Filaggrin [FLG], caspase 14, and keratin 10) in human primary keratinocytes. Interestingly, both acetyl dipeptide 1 cetyl ester (active D) and niacinamide (active C) improved dermal gene expression (fibrillin-1, Collagen type 1 alpha 1, Decorin, Lysyl oxidase-like 1) and, moreover, had significant anti-glycant and proteasomal promoter activity in human primary fibroblasts. CONCLUSION: Considering consumers need in heavily polluted areas, we developed a multipurpose formulation comprised of unique active complexes toward pollution, pollution induced inflammation, skin brightening, and antiaging concerns with beneficial results demonstrated by in vitro and ex vivo studies.

ID1 Is Critical for Tumorigenesis and Regulates Chemoresistance in Glioblastoma.

Glioblastoma is the most common primary brain tumor in adults. While the introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid tumor recurrence remains universal. The transcriptional regulatory protein, inhibitor of DNA-binding-1 (ID1), is a key regulator of cell phenotype in cancer. We show that CRISPR-mediated knockout of ID1 in glioblastoma cells, breast adenocarcinoma cells, and melanoma cells dramatically reduced tumor progression in all three cancer systems through transcriptional downregulation of EGF, which resulted in decreased EGFR phosphorylation. Moreover, ID1-positive cells were enriched by chemotherapy and drove tumor recurrence in glioblastoma. Addition of the neuroleptic drug pimozide to inhibit ID1 expression enhanced the cytotoxic effects of temozolomide therapy on glioma cells and significantly prolonged time to tumor recurrence. Conclusively, these data suggest ID1 could be a promising therapeutic target in patients with glioblastoma. SIGNIFICANCE: These findings show that the transcriptional regulator ID1 is critical for glioblastoma initiation and chemoresistance and that inhibition of ID1 enhances the effect of temozolomide, delays tumor recurrence, and prolongs survival.

Anti-cancer stem cell activity of a sesquiterpene lactone isolated from Ambrosia arborescens and of a synthetic derivative.

New regimens are constantly being pursued in cancer treatment, especially in the context of treatment-resistant cancer stem cells (CSCs) that are assumed to be involved in cancer recurrence. Here, we investigated the anti-cancer activity of sesquiterpene lactones (SLs) isolated from Ambrosia arborescens and of synthetic derivatives in breast cancer cell lines, with a specific focus on activity against CSCs. The breast cancer cell lines MCF-7, JIMT-1, and HCC1937 and the normal-like breast epithelial cell line MCF-10A were treated with the SLs damsin and coronopilin, isolated from A. arborescens, and with ambrosin and dindol-01, synthesized using damsin. Inhibitory concentration 50 (IC50) values were obtained from dose-response curves. Based on IC50 values, doses in the µM range were used for investigating effects on cell proliferation, cell cycle phase distribution, cell death, micronuclei formation, and cell migration. Western blot analysis was used to investigate proteins involved in cell cycle regulation as well as in the NF-κB pathway since SLs have been shown to inhibit this transcription factor. Specific CSC effects were investigated using three CSC assays. All compounds inhibited cell proliferation; however, damsin and ambrosin were toxic at single-digit micromolar ranges, while higher concentrations were required for coronopilin and dindol-01. Of the four cell lines, the compounds had the least effect on the normal-like MCF-10A cells. The inhibition of cell proliferation can partly be explained by downregulation of cyclin-dependent kinase 2. All compounds inhibited tumour necrosis factor-α-induced translocation of NF-κB from the cytoplasm to the nucleus. Damsin and ambrosin treatment increased the number of micronuclei; moreover, another sign of DNA damage was the increased level of p53. Treatment with damsin and ambrosin decreased the CSC subpopulation and inhibited cell migration. Our results suggest that these compounds should be further investigated to find efficient CSC-inhibiting compounds.

Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047.

Cancer stem cells (CSCs) are considered to be of particular concern in cancer as they possess inherent properties of self-renewal and differentiation, along with expressing certain genes related to a mesenchymal phenotype. These features favour the promotion of tumour recurrence and metastasis in cancer patients. Thus, the optimal chemotherapeutic treatment should target the CSC population, either by killing these cells and/or by inducing their transition to a more differentiated epithelial-like phenotype. Experiments were carried out on the trastuzumab-resistant human epidermal growth factor receptor 2-overexpressing breast cancer cell line JIMT-1 to unravel the chemotherapeutic effects of the polyamine analogue [1N,12N]bis(ethyl)-cis-6,7-dehydrospermine (PG11047) and of the polyamine biosynthetic inhibitor 2-difluoromethylornithine (DFMO) on the CD44+CD24- CSC population. Furthermore, effects on the properties of self-renewal and epithelial/mesenchymal markers were also investigated. Treatment with PG11047 reduced the CD44+CD24- subpopulation of JIMT-1 cells by approximately 50%, inhibited and/or reduced self-renewal capability of the CSC population, decreased cell motility and induced expression of mesenchymal to epithelial transition-associated proteins that are involved in promoting an epithelial phenotype. By contrast, DFMO slightly increased the CD44+CD24- subpopulation, increased cell motility and the level of mesenchymal-related proteins. DFMO treatment reduced the self-renewal capability of the CSC population. Both PG11047 and DFMO reduced the expression of the human epidermal growth factor receptor 2 protein, which is correlated to malignancy and resistance to trastuzumab in JIMT-1 cells. Our findings indicate that treatment with PG11047 targeted the CSC population by interfering with several stem cell-related properties, such as self-renewal, differentiation, motility and the mesenchymal phenotype.