Argumentation in anonymous online discussions about decriminalising cannabis use.

Aims: In October 2019, a citizens' initiative to decriminalise cannabis use started a large debate about drug policy in Finland. This study examines online discussions about the initiative to supplement the current knowledge about citizens' drug opinions. The focus is especially on argumentation techniques that are used to support or object to the decriminalisation. Design: Methodologically, the study is based on discourse studies, new rhetoric, and argumentation analysis. The data of 1,092 messages were collected from a popular Finnish anonymous discussion forum Ylilauta. Results: Online discussions about the legal status of cannabis are highly polarised. Decriminalisation is often both supported and resisted in a strong and affective manner, and even hate speech is not rare in the data. Statements made by both discussion parties often lack any argumentation or are based on fallacies, especially ad hominem arguments. Some discussants refer to scientific studies and expert statements, even though such references are usually inaccurate. Cannabis is compared to alcohol more often than to other illegal drugs. Conclusions: The emotional responses and inadequate argumentation might be partially explained by the general nature of online discussions and the culture of the investigated website, but also by the powerful stigma related to illegal drugs and insufficient knowledge on the subject. A future objective is to create a societal atmosphere where the complex question of the legal status of cannabis could be discussed more neutrally and rationally.

Alterations in the expression of EMT-related proteins claudin-1, claudin-4 and claudin-7, E-cadherin, TWIST1 and ZEB1 in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a chronic T-cell-mediated inflammatory disease, which is associated with increased risk of developing oral squamous cell carcinoma. Epithelial-to-mesenchymal transition is a physiological phenomenon occurring during growth and organogenesis, but it has also an important role in tumorigenesis. In the present work, we studied the expression of known epithelial-to-mesenchymal transition markers in oral lichen planus. METHODS: In total, 54 oral lichen planus and 22 control samples were analyzed for epithelial-to-mesenchymal transition markers. Samples were immunohistochemically stained for claudin-1, claudin-4 and claudin-7, cadherin-1 (E-cadherin), Twist-related protein 1 (TWIST1) and zinc finger E-box-binding homeobox 1 (ZEB1). RESULTS: The expression of claudin-1, claudin-4 and E-cadherin was significantly weaker in oral lichen planus epithelium compared to controls (P < 0.001). The quantity of claudin-7-expressing cells (P < 0.001) and claudin-7 staining intensity (P < 0.05) in the stroma was greater in lichen planus than in control samples. TWIST1 and ZEB1 stainings were negative in the epithelium in both lichen planus and controls. The number of TWIST1-expressing cells in the stroma was higher in lichen planus than in controls (P < 0.001). There was a statistically significant difference in ZEB1 staining intensity in the stroma between lichen planus and control samples (P < 0.05). CONCLUSIONS: The data indicate that the expression of claudin-1, claudin-4 and E-cadherin is decreased in oral lichen planus. This may lead to disturbance in epithelial tight junctions, cell-cell connections and epithelial permeability, contributing to oral lichen planus pathogenesis. Based on the present study, the role of TWIST1 and ZEB1 in oral lichen planus remains unclear.

The organic osmolyte betaine induces keratin 2 expression in rat epidermal keratinocytes - A genome-wide study in UVB irradiated organotypic 3D cultures.

The moisturizing and potentially protective properties of the organic osmolyte betaine (trimethylglycine) have made it an attractive component for skin care products. Its wide use despite the lack of comprehensive studies addressing its specific effects in skin led us to characterize the molecular targets of betaine in keratinocytes and to explore, whether it modifies the effects of acute UVB exposure. Genome-wide expression analysis was performed on organotypic cultures of rat epidermal keratinocytes, treated either with betaine (10mM), UVB (30 mJ/cm(2)) or their combination. Results were verified with qRT-PCR, western blotting and immunohistochemistry. Additionally, cell proliferation and differentiation were analyzed. Among the 89 genes influenced by betaine, the differentiation marker keratin 2 showed the highest upregulation, which was also confirmed at protein level. Expression of Egr1, a transcription factor, and Purkinje cell protein 4, a regulator of Ca(2+)/calmodulin metabolism, also increased, while downregulated genes included several ion-channel components, such as Fxyd2. Bioinformatics analyses suggest that genes modulated by betaine are involved in DNA replication, might counteract UV-induced processes, and include many targets of transcription factors associated with cell proliferation and differentiation. Our results indicate that betaine controls unique gene expression pathways in keratinocytes, including some involved in differentiation.

Low dose ultraviolet B irradiation increases hyaluronan synthesis in epidermal keratinocytes via sequential induction of hyaluronan synthases Has1-3 mediated by p38 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling.

Hyaluronan, a major epidermal extracellular matrix component, responds strongly to different kinds of injuries. This also occurs by UV radiation, but the mechanisms involved are poorly understood. The effects of a single ultraviolet B (UVB) exposure on hyaluronan content and molecular mass, and expression of genes involved in hyaluronan metabolism were defined in monolayer and differentiated, organotypic three-dimensional cultures of rat epidermal keratinocytes. The signals regulating the response were characterized using specific inhibitors and Western blotting. In monolayer cultures, UVB increased hyaluronan synthase Has1 mRNA already 4 h postexposure, with a return to control level by 24 h. In contrast, Has2 and Has3 were persistently elevated from 8 h onward. Silencing of Has2 and especially Has3 decreased the UVB-induced accumulation of hyaluronan. p38 and Ca(2+)/calmodulin-dependent protein kinase II pathways were found to be involved in the UVB-induced up-regulation of Has2 and Has3 expression, respectively, and their inhibition reduced hyaluronan deposition. However, the expressions of the hyaluronan-degrading enzymes Hyal1 and Hyal2 and the hyaluronan receptor Cd44 were also up-regulated by UVB. In organotypic cultures, UVB treatment also resulted in increased expression of both Has and Hyal genes and shifted hyaluronan toward a smaller size range. Histochemical stainings indicated localized losses of hyaluronan in the epidermis. The data show that exposure of keratinocytes to acute, low dose UVB increases hyaluronan synthesis via up-regulation of Has2 and Has3. The simultaneously enhanced catabolism of hyaluronan demonstrates the complexity of the UVB-induced changes. Nevertheless, enhanced hyaluronan metabolism is an important part of the adaptation of keratinocytes to radiation injury.