RESUMEN
Background: Post-stroke dementia may affect up to one-third of stroke survivors. Acupuncture as a complementary treatment for stroke has been shown to be beneficial for subsequent post-stroke rehabilitation. The purpose of this retrospective cohort study was to investigate the potential effect of acupuncture to protect stroke patients from dementia. Methods: We included 9,547 patients receiving ambulatory or hospital care for stroke and 9.547 non-stroke patients; patients were matched for sex, age, and Charlson Comorbidity Index. Each individual was traced for the subsequent development of dementia. Two thousand four hundred and forty-nine stroke patients received acupuncture treatment and 7,098 residue stroke patients without acupuncture treatment served as control groups. This is a 3-year follow-up cohorts study: the incidence and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of post- stroke dementia in the Cox proportional hazard regression. Results: During the 3-year follow-up, 1,403 patients with stroke (14.70%) and 427 patients without stroke (4.47%) developed dementia. The adjusted HRs of development of dementia among stroke patients were 3.64-times (range, 3.27-4.06), and the incidence of dementia was higher in male. Stroke patients receiving acupuncture treatment had a lower probability of dementia than those without acupuncture during the follow-up period, the adjusted HRs was 0.49 (95% CI, 0.42-0.58; p < 0.001). Conclusions: The association between stroke and dementia existed in both sexes, more prominent in male. Patients with stroke receiving acupuncture treatments showed decreased risk of dementia. Care must be taken evaluating these results because this study was limited to lack of information regarding lifestyles, stroke severities, and acupuncture methods that were used in treatments.
RESUMEN
Epigallocatechin gallate (EGCG) from green tea can induce apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Using SPR and NMR, here we report a direct, µM interaction between EGCG and the tumor suppressor p53 (KD = 1.6 ± 1.4 µM), with the disordered N-terminal domain (NTD) identified as the major binding site (KD = 4 ± 2 µM). Large scale atomistic simulations (>100 µs), SAXS and AUC demonstrate that EGCG-NTD interaction is dynamic and EGCG causes the emergence of a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupts p53 interaction with its regulatory E3 ligase MDM2 and inhibits ubiquitination of p53 by MDM2 in an in vitro ubiquitination assay, likely stabilizing p53 for anti-tumor activity. Our work provides insights into the mechanisms for EGCG's anticancer activity and identifies p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.