Understanding the Phytoestrogen Genistein Actions on Breast Cancer: Insights on Estrogen Receptor Equivalence, Pleiotropic Essence and Emerging Paradigms in Bioavailability Modulation.

Prevalent as a major phenolic ingredient of soy and soy products, genistein is recognized as an eminent phytoestrogen owing to its interacting ability with estrogen receptors (ERs). The metabolic conversion of plant-derived genistin to genistein by gut microbes and intestinal enzymes enhances its absorption at intestinal pH of ~7.5-7.8. Genistein interferes in breast cancer (BC) development via pleiotropic actions on cell proliferation, survival, angiogenesis, and apoptosis. Though multiple investigations have demonstrated genistein intake-driven reduced BC risk, similar efficacy has not been replicated in clinical trials. Furthermore, multiple studies have structurally and functionally equated genistein extents with 17-ß-estradiol (E2), the most available physiological estrogen in females, culminating in aggravated BC growth. Of note, both genistein and E2 function via interacting with ERs (ERα and ERß). However, although E2 shows almost equal affinity towards both ERα and ERß, genistein shows more affinity towards ERß than ERα. Our cautious literature survey revealed typical intake mode, ER expression pattern and the ratio of ERα and ERß, transactivators/ regulators of ERα and ERß expression and activities, patient age, and menopausal status as decisive factors affecting genistein BC activities. Of further interest are the mechanisms by which genistein inhibits triple-negative breast cancers (TNBCs), which lack ERs, progesterone receptors (PRs), and human epidermal growth factor receptors (HER2). Herein, we attempt to understand the dosage-specific genistein actions in BC cells and patients with an insight into its better response via derivative development, nanocarrier-assisted, and combinatorial delivery with chemotherapeutic drugs.

Elevated pulmonary artery systolic pressures are associated with a lower risk of atrial fibrillation following lung transplantation.

BACKGROUND: Atrial fibrillation (AF) is common after open-chest procedures, but the etiology remains poorly understood. Lung transplant procedures allow for the study of novel contributing factors. METHODS: Records of lung transplant procedures performed at a single center between 2002 and 2009 were reviewed. RESULTS: Of 174 patients, 27 (16%) had AF a median 6 days post-surgery. Post-operative AF patients less often had right ventricular hypertrophy (RVH) by either electrocardiogram (0 versus 14%, P=.042) or echocardiography (19% versus 47%, P=.006), and had lower pulmonary artery systolic pressures (PASP) (39 ± 12 versus 51 ± 22, P=.005). After multivariable adjustment, every 10-mm Hg increase in PASP was associated with a 31% reduction in the odds of post-operative AF (OR 0.69, 95% CI 0.49-0.98, P=.035). A higher pulmonary pressure was the only predictor independently associated with less post-operative AF. CONCLUSIONS: Higher PASP was associated with a lower risk of AF after lung transplantation.