Kirkebyheller3460
Oleuropein (OLE) and hydroxytyrosol (HT) are olive-derived phenols recognised as health-promoting agents with antioxidant, anti-inflammatory, cardioprotective, antifungal, antimicrobial, and antitumor activities, providing a wide range of applications as functional food ingredients. HT is Generally Recognised as Safe (GRAS) by the European Food Safety Authority (EFSA) and the Food and Drug Administration (FDA), whereas OLE is included in EFSA daily consumptions recommendations, albeit there is no official GRAS status for its pure form. Their application in food, however, may be hindered by challenges such as degradation caused by processing conditions and undesired sensorial properties (e.g., the astringency of OLE). Among the strategies to overcome such setbacks, the encapsulation in delivery systems and the covalent and non-covalent complexation are highlighted in this review. Additionally, the synthesis of OLE and HT derivatives are studied to improve their applicability. All in all, more research needs however to be carried out to investigate the impact of these approaches on the sensory properties of the final food product and its percussions at the gastrointestinal level, as well as on bioactivity. At last limitations of these approaches at a scale of the food industry must also be considered.Trifluoperazine (TFP), an antipsychotic drug approved by the Food and Drug Administration, has been show to exhibit anti-cancer effects. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by a progressive obliteration of small pulmonary arteries (PAs) due to exaggerated proliferation and resistance to apoptosis of PA smooth muscle cells (PASMCs). However, the therapeutic potential of TFP for correcting the cancer-like phenotype of PAH-PASMCs and improving PAH in animal models remains unknown. PASMCs isolated from PAH patients were exposed to different concentrations of TFP before assessments of cell proliferation and apoptosis. The in vivo therapeutic potential of TFP was tested in two preclinical models with established PAH, namely the monocrotaline and sugen/hypoxia-induced rat models. Assessments of hemodynamics by right heart catheterization and histopathology were conducted. TFP showed strong anti-survival and anti-proliferative effects on cultured PAH-PASMCs. Exposure to TFP was associated with downregulation of AKT activity and nuclear translocation of forkhead box protein O3 (FOXO3). In both preclinical models, TFP significantly lowered the right ventricular systolic pressure and total pulmonary resistance and improved cardiac function. Consistently, TFP reduced the medial wall thickness of distal PAs. Overall, our data indicate that TFP could have beneficial effects in PAH and support the view that seeking new uses for old drugs may represent a fruitful approach.Diffuse Intrinsic Pontine Gliomas (DIPGs) are highly aggressive paediatric brain tumours. Currently, irradiation is the only standard treatment, but is palliative in nature and most patients die within 12 months of diagnosis. Novel therapeutic approaches are urgently needed for the treatment of this devastating disease. We have developed non-persistent gold nano-architectures (NAs) functionalised with human serum albumin (HSA) for the delivery of doxorubicin. Doxorubicin has been previously reported to be cytotoxic in DIPG cells. In this study, we have preclinically evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoarchitectures (NAs-HSA-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and doxorubicin-loaded NAs. AT7519 Colony formation assays demonstrated greater potency of NAs-HSA-Dox on colony formation compared to doxorubicin. Western blot analysis indicated increased apoptotic markers cleaved Parp, cleaved caspase 3 and phosphorylated H2AX in NAs-HSA-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of NAs-HSA-Dox into DIPG neurospheres compared to doxorubicin alone. Despite the potency of the NAs in vitro, treatment of an orthotopic model of DIPG showed no antitumour effect. This disparate outcome may be due to the integrity of the blood-brain barrier and highlights the need to develop therapies to enhance penetration of drugs into DIPG.The paper reports on the properties of UV-curable inorganic-organic hybrid polymer multimode optical channel waveguides fabricated by roll-to-plate (R2P) nanoimprinting. We measured transmission spectra, refractive indices of the applied polymer materials, and optimized the R2P fabrication process. Optical losses of the waveguides were measured by the cut-back method at wavelengths of 532, 650, 850, 1310, and 1550 nm. The lowest optical losses were measured at 850 nm and the lowest average value was 0.19 dB/cm, and optical losses at 1310 nm were 0.42 dB/cm and 0.25 dB/cm at 650 nm respectively. The study has demonstrated that nanoimprinting has great potential for the implementation of optical polymer waveguides not only for optical interconnection applications.This systematic review sheds light on the effectiveness of auditory-verbal therapy (AVT) outcomes in children with cochlear implants (CIs). The presented outcome is based on research findings from the last 10 years. The systematic review was designed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Critical Appraisal of Treatment Evidence (CATE) checklist. Specific keywords were chosen based on the research question and searched on the PubMed database. All searched papers were analysed based on specific exclusion criteria and classified into four evidence levels. The results revealed that children who participated in AV therapy can achieve linguistic skills at the same level as their hearing peers. Voice quality seemed positively affected, placing young children with CIs in the normal range for receptive vocabulary development. In contrast, reading skills seemed less benefited. AV therapy seems to contribute to integration into mainstream society. Despite the recorded speech and language improvements of young children with CIs, the aim of AV therapy is still not fulfilled. AV therapy can be seen as the best clinical practice for young children with CIs till now, but the lack of well-controlled studies is undermining.