Boswellic acid formulations are not suitable for treatment of pediatric high-grade glioma due to tumor promoting potential.

Background and aim: Pediatric high-grade gliomas (pedHGG) comprise a very poor prognosis. Thus, parents of affected children are increasingly resorting to complementary and alternative medicine (CAM), among those Boswellia extracts. However, nothing is known about the therapeutic effectiveness of their active substances, Boswellic acids (BA) in pedHGG. Thus, we aimed to investigate if the three main Boswellic acids (BA) present in Boswellia plants, alpha-boswellic acid (α-BA), beta-boswellic acid (ß-BA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA) hold any promising potential for treatment of affected pedHGG patients. Experimental procedure: Histone 3 (H3)-wildtype and H3.3K27M-mutant pedHGG cell lines were treated with BA, either alone or in combination with radio-chemotherapy with temozolomide. Cell viability, stemness properties, apoptosis, in ovo tumor growth and the transcriptome was investigated upon BA treatment. Results and conclusion: Interestingly, α-BA and ß-BA treatment promoted certain tumor properties in both pedHGG cells. AKBA treatment reduced cell viability and colony growth accompanied by induction of slight anti-inflammatory effects especially in H3.3K27M-mutant pedHGG cells. However, no effects on apoptosis and in ovo tumor growth were found. In conclusion, besides positive anti-tumor effects of AKBA, tumor promoting effects were observed upon treatment with α-BA and ß-BA. Thus, only pure AKBA formulations may be used to exploit any potential positive effects in pedHGG patients. In conclusion, the use of commercially available supplements with a mixture of different BA cannot be recommended due to detrimental effects of certain BA whereas pure AKBA formulations might hold some potential as therapeutic supplement for treatment of pedHGG patients.

Nurses' Quality of Life and Healthy Behaviors.

Quality of life (QoL) is closely linked to the health status of the individual. In turn, health status strongly depends on lifestyle. Health behavior, which is defined as the actions and attitudes of a person that affect their physical and mental health, is one of many lifestyle components. The nursing community, which is exposed to a range of dangers associated with the job position and responsibilities of the nursing profession, has to contend with several negative impacts. This results in a decreased quality of life among the nursing staff and reduced effectiveness in providing care services to patients. METHODS: This study was conducted using an online Google questionnaire, which was completed by 312 nurses nationwide. The questionnaire included questions about the respondents' socio-demographic survey and included the Health Behavior Inventory (HBI) by Juczynski and the WHOQoL-BREF questionnaire. RESULTS: The mean QoL reported by respondents was 3.65 points (SD = 0.67), meaning that QoL ranked between good and average results. The respondents' mean rating of their own health was 3.58 points (SD = 0.79), indicating that they rated their health status between satisfactory and average. Low health-behavior prevalence was reported by 139 of the 312 survey participants (44.55%), while 111 respondents (35.58%) had average health-behavior prevalence and 62 (19.87%) had high health-behavior prevalence. Each of the QoL domains correlated significantly (p ˂ 0.05) and positively (r ˃ 0) with the total HBI score and all its subscales. CONCLUSIONS: Higher quality of life improves the level of health behavior by nursing staff. Obesity lowers the quality of life in physical, psychological, and social domains. The psychological sphere was the best-rated quality of life domain by nurses. A good material situation for nurses has a positive effect on their quality of life.

Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells.

Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes. The activity of the acetyltransferase CREB-binding protein (CBP) is enhanced by BRD4 and associated with acetylation of nucleosomes at super enhancers (SE). In addition, CBP contributes to transcriptional activation through its function as a scaffold and protein bridge. Monotherapy with either a CBP (ICG-001) or BET inhibitor (JQ1) led to the reduction of tumor-related characteristics. Interestingly, combined treatment induced strong cytotoxic effects in H3.3K27M-mutated DIPG cell lines. RNA sequencing and chromatin immunoprecipitation revealed that these effects were caused by the inactivation of DIPG SE-controlled tumor-related genes. However, single treatment with ICG-001 or JQ1, respectively, led to activation of a subgroup of detrimental super enhancers. Combinatorial treatment reversed the inadvertent activation of these super enhancers and rescued the effect of ICG-001 and JQ1 single treatment on enhancer-driven oncogenes in H3K27M-mutated DIPG, but not in H3 wild-type pedHGG cells. In conclusion, combinatorial treatment with CBP and BET inhibitors is highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy.