AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis.
MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model.
RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor.
CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.
METHODS: Data from the Global Burden of Disease Study (GBD) 2019 were analyzed, adopting Sawyer's broad definition of adolescence encompassing ages 10 to 24. Estimated annual percentage changes (EAPCs) were used to assess temporal trends.
RESULTS: Globally, from 1990 to 2019, there was a decrease in the ASIR of depression in adolescents (EAPC = -0.23). Notably, this decrease was more pronounced in female adolescents compared to their male counterparts (EAPC = -0.12 and - 0.29, respectively). Conversely, high Sociodemographic Index (SDI) regions experienced a significant increase in the ASIR of depression among adolescents (EAPC = 0.87). Furthermore, it is worth mentioning that individuals aged 20-24 exhibited the highest incidence rate for depression followed by those aged 15-19 and then those aged 10-14. The largest increases in the ASIRs of depression occurred in High-income North America (EAPC = 1.19) and Malaysia (EAPC = 2.4), respectively.
LIMITATIONS: Mathematical models were used to reconstruct and adjust data of different qualities, which might have introduced bias.
CONCLUSIONS: The global burden of disease for depression among adolescents aged 10-24 years declined from 1990 to 2019. Special attention must be paid to older adolescents and areas with higher SDIs.
METHODS: A total of 236 breast cancer patients from China completed the Chinese Version of the Posttraumatic Stress Disorder Symptom Scale (PSS), the Chinese version of the Patient Health Questionnaire (PHQ-9), the Chinese version of the General Anxiety Symptoms Scale (GAD-7). In addition, caregivers of these breast cancer patients were surveyed by the Caregiver Self-Assessment Questionnaire (CSAQ).
RESULTS: Structural equation model showed that our model fitted well [χ2 /df = 1.966, TLI = 0.959, CFI = 0.994, RMSEA (90% CI) = 0.065 (0-0.12)] and revealed that anxiety, but not depression, mediated the relationship between PTSS in breast cancer patients and caregiver burden.
CONCLUSION: The level of PTSS was positively correlated with anxiety and depression in breast cancer patients, and the level of anxiety and depression was positively related to caregiver burden. The PTSS of patients positively predicted caregiver burden and this relationship appears to be mediated by the patient's anxiety.