Beta Elemene induces cytotoxic effects in FLT3 ITD-mutated acute myeloid leukemia by modulating apoptosis.

OBJECTIVE: ß-Elemene, a sesquiterpene with a broad anti-cancer spectrum, is particularly effective against drug-resistant and complex tumors. It can also be efficient against FLT3-expressed acute myeloid leukemia. This research aims to determine whether ß-Elemene has cytotoxic effects on FLT3 ITD-mutated AML cells. MATERIALS AND METHODS: Cytotoxicity, cell morphology, mRNA analysis with apoptotic markers, and analysis of 43 distinct protein markers related to cell death, survival, and resistance were all performed to elucidate its mechanism. Additionally, in order to understand how ß-Elemene and FLT3 interact, molecular docking, molecular dynamics simulations, and computational ADME investigations were performed. RESULTS: ß-Elemene exhibited cytotoxic activity against FLT3-mutated MV4-11 and FLT3 wild-type THP-1 cells, with an IC50 of around 25 µg/ml. The molecular studies revealed that ß-Elemene inhibited cell proliferation by inducing p53, and the involvement of p21, p27, HTRA, and HSPs were also demonstrated. The interactive inhibition in proliferation was confirmed via molecular docking and dynamics analyses. ß-Elemene occupied the FLT3 enzymatic pocket with good stability at the FLT3 active site. CONCLUSIONS: We concluded from our observations that ß-Elemene causes cell death in ITD mutant AML cells, together with the effects of stress factors and inhibiting cell division.

Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azide-alkyne cycloadditions.

Copper(I)-catalyzed azide-alkyne cycloaddition has become a commonly employed method for the synthesis of complex molecular architectures under challenging conditions. Despite the widespread use of copper-catalyzed cycloaddition reactions, the mechanism of these processes has remained difficult to establish due to the involvement of multiple equilibria between several reactive intermediates. Real-time monitoring of a representative cycloaddition process via heat-flow reaction calorimetry revealed that monomeric copper acetylide complexes are not reactive toward organic azides unless an exogenous copper catalyst is added. Furthermore, crossover experiments with an isotopically enriched exogenous copper source illustrated the stepwise nature of the carbon-nitrogen bond-forming events and the equivalence of the two copper atoms within the cycloaddition steps.

Assessing diabetes support in adolescents: factor structure of the modified Diabetes Social Support Questionnaire (DSSQ-Friends).

AIMS: To determine the underlying factor structure of friends' enacted support behaviours for adolescents with Type 1 diabetes, confirm it in a second sample, delineate distinctive aspects of friends' support and test the reliability of resulting scale. METHODS: The study included a total of 434 adolescents (54.8% girls), mean age 14.7 years, mean duration of diabetes 6.1 years. RESULTS: Results from the exploratory factor analysis, including data from a random half of the participants revealed a five-factor solution explaining approximately 48.4% of the item variance. The five factors emerged Guidance and Encouragement (13 items; α=0.91), Help in Critical Situations (7 items; α=0.92), Nourishment (11 items; α=0.88), Empathy (6 items; α=0.83) and Help in Exercise (5 items; α=0.76). Confirmatory factor analysis on the remainder of the sample showed good indices of model fit. Comparison of the factor structure across gender and age also presented an excellent fit. In a second-order factor analysis all five factors loaded on one overall factor, Diabetes Social Support-Friends. Construct validity of the resulting scales was supported by predicted associations of Modified Diabetes Specific Support Questionnaire-Friends scale scores with HbA(1c) , treatment adherence and responsibility, and well-being. CONCLUSION: The 42-item Modified Diabetes Specific Support Questionnaire-Friends emerged as a reliable and valid scale for Dutch adolescents with Type 1 diabetes and measures five factors of diabetes-specific support from close friends.

Association between impulsivity, reward responsiveness and body mass index in children.

BACKGROUND: Childhood obesity is a major health problem. An association between children's body mass index (BMI) and overeating has been established, but mechanisms leading to overeating are poorly understood. The personality characteristics impulsivity and reward responsiveness may be involved in the tendency to overeat. Impulsivity might relate to overeating through poor inhibition of food intake; reward responsiveness through the rewarding value of food. OBJECTIVE: This study aimed to reveal the relationships between impulsivity, reward responsiveness, overeating and BMI in a sample of 346 Dutch children aged 6-13 years. The BMI distribution in the sample was representative of the BMI distribution in the Dutch pediatric population. METHODS: Impulsivity and reward responsiveness were measured with the Dutch version of the parent-report Sensitivity to Punishment and Sensitivity to Reward Questionnaire for children. Overeating was assessed with the Dutch translation of the parent-report Children's Eating Behaviour Questionnaire. RESULTS: Overeating, impulsivity and reward responsiveness were significantly associated with childhood BMI. Mediation analysis revealed that impulsivity and reward responsiveness equally and significantly predicted BMI indirectly through overeating. CONCLUSIONS: The personality characteristics impulsivity and reward responsiveness predict childhood BMI indirectly through overeating. This suggests that these personality characteristics are risk factors for obesity.

Giant prolactinoma causing cranio-cervical junction instability: a case report.

Prolactinomas are common secretory pituitary tumours, usually managed with dopamine agonists. There have previously been case reports of rarer giant prolactinomas causing invasion of surrounding structures. We describe a case report of an exceptionally aggressive giant prolactinoma that eroded the occipital condyles causing cranio-cervical joint instability mandating surgical fixation.

Impact of aorto-coronary graft markers on subsequent graft patency: a retrospective review.

The use of aorto-coronary graft markers has not been standard, presumably due to concern about possible adverse effects on subsequent graft patency. Our goal was to determine if there was any increased risk of graft occlusion in patients who received circumferential graft markers at the time of their coronary artery bypass (CAB) surgery. A retrospective review of angiograms was performed for patients with prior CAB. Cohorts with and without graft markers were compared. A total of 405 "unmarked" and 311 "marked" grafts were identified in 335 patients meeting inclusion criteria. Patency is reported in divisions of elapsed time since CAB. Overall patency in the "marked" group (71.1%) was significantly higher than in the "unmarked" group (58.0%, P < 0.001). In this retrospective population, there was no increased risk of graft occlusion in patients who received circumferential graft markers at the time of CAB surgery as compared to those patients who did not.