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Background: Orthorexia nervosa (ON), or the obsessive desire to eat only healthy foods, is closely linked to eating behaviors. Among adolescents, the risk of developing ON and its consequences, including weight loss and malnutrition, can be particularly significant due to the crucial impact of eating behaviors on an individual's psychophysical development., Objective: The aim of the study was to examine the relationship between the eating behaviors of high school students and the risk of ON., Material and Methods: Observational study was conducted using the PAPI method among 514 students aged 14-19, of which 59.3% (N=305) were female. The research tool was a proprietary, validated questionnaire that included the ORTO-15 test (cutoff score=35) and the BSQFVF. The questionnaire was used to assess the frequency of consumption of selected food products, the level of dietary fiber intake, the quantity and regularity of meals consumed, as well as other eating behaviors of the participants. The individual responses were then analyzed according to the risk of ON using correlation coefficients., Results: The prevalence of ON risk was found to be 32.1% (N=165). The percentage of individuals at risk of ON was higher among vegetarians. The results regarding the frequency of consumption of animal protein sources, dietary fiber intake, the number of meals and their regularity were similar in both the group at risk of ON and the group not at risk. Over 80% of individuals who never consumed bars, gummies, and candies were at risk of developing ON., Conclusions: The risk of ON was higher among vegetarians. Individuals who excluded highly processed foods from their diet were more susceptible to developing ON.

AXL, a TAM receptor tyrosine kinase (RTK), and its ligand growth arrest-specific 6 (GAS6) are implicated in cancer metastasis and drug resistance, and cellular entry of viruses. Given this, AXL is an attractive therapeutic target, and its inhibitors are being tested in cancer and COVID-19 clinical trials. Still, astonishingly little is known about intracellular mechanisms that control its function. Here, we characterized endocytosis of AXL, a process known to regulate intracellular functions of RTKs. Consistent with the notion that AXL is a primary receptor for GAS6, its depletion was sufficient to block GAS6 internalization. We discovered that upon receptor ligation, GAS6-AXL complexes were rapidly internalized via several endocytic pathways including both clathrin-mediated and clathrin-independent routes, among the latter the CLIC/GEEC pathway and macropinocytosis. The internalization of AXL was strictly dependent on its kinase activity. In comparison to other RTKs, AXL was endocytosed faster and the majority of the internalized receptor was not degraded but rather recycled via SNX1-positive endosomes. This trafficking pattern coincided with sustained AKT activation upon GAS6 stimulation. Specifically, reduced internalization of GAS6-AXL upon the CLIC/GEEC downregulation intensified, whereas impaired recycling due to depletion of SNX1 and SNX2 attenuated AKT signaling. Altogether, our data uncover the coupling between AXL endocytic trafficking and AKT signaling upon GAS6 stimulation. Moreover, our study provides a rationale for pharmacological inhibition of AXL in antiviral therapy as viruses utilize GAS6-AXL-triggered endocytosis to enter cells., (© 2022. The Author(s).)

AXL, a receptor tyrosine kinase from the TAM (TYRO3 AXL and MER) subfamily, and its ligand growth arrest-specific 6 (GAS6) are implicated in pathogenesis of a wide array of cancers, acquisition of resistance to diverse anticancer therapies and cellular entry of viruses. The continuous development of AXL inhibitors for treatment of patients with cancer and COVID-19 underscores the need to better characterize the cellular effects of AXL targeting., In the present study, we compared the cellular phenotypes of CRISPR-Cas9-induced depletion of AXL and its pharmacological inhibition with bemcentinib, LDC1267 and gilteritinib. Specifically, we evaluated GAS6-AXL signaling, cell viability and invasion, the endo-lysosomal system and autophagy in glioblastoma cells. We showed that depletion of AXL but not of TYRO3 inhibited GAS6-induced phosphorylation of downstream signaling effectors, AKT and ERK1/2, indicating that AXL is a primary receptor for GAS6. AXL was also specifically required for GAS6-dependent increase in cell viability but was dispensable for viability of cells grown without exogenous addition of GAS6. Furthermore, we revealed that LDC1267 is the most potent and specific inhibitor of AXL activation among the tested compounds. Finally, we found that, in contrast to AXL depletion and its inhibition with LDC1267, cell treatment with bemcentinib and gilteritinib impaired the endo-lysosomal and autophagy systems in an AXL-independent manner., Implications: Altogether, our findings are of high clinical importance as we discovered that two clinically advanced AXL inhibitors, bemcentinib and gilteritinib, may display AXL-independent cellular effects and toxicity., (©2021 American Association for Cancer Research.)