Mixed-monolayer functionalized gold nanoparticles for cancer treatment: Atomistic molecular dynamics simulations study.

Gold nanoparticles (AuNPs) are employed as drug carriers due to their inertness, non-toxicity, and ease of synthesis. An experimental search for the optimal AuNP design would require a systematic variation of physico-chemical properties which is time-consuming and expensive. Computational methods provide quicker and cheaper approach to complement experiments and provide useful guidelines. In this paper, we performed atomistic molecular dynamics simulations to study how the size, hydrophobicity, and concentration of the drug affect the structure of functionalized AuNPs in the aqueous environment. We simulated two groups of nano-systems functionalized with a zwitterionic background ligand, and a ligand carrying a drug (Quinolinol or Panobinostat). Results indicate that in the case of a hydrophobic drug (Quinolinol), the hydrophobicity drives the conformation changes of the coating layer. The tendency of the hydrophobic drug to reduce its solvent-accessible surface results in a decrease of the coating thickness and the overall NP size. Although the amount of accessible drug can be increased by increasing its initial concentration, it will compromise the solubility of the system. In the case of a hydrophilic drug (Panobinostat), the ligand in excess has a dominant influence on the final structure of the coating conformations. The percentage of accessible drug is significantly higher than in the hydrophobic systems for any given ratio. It implies that for hydrophilic systems we can generally expect higher biological efficiency. Our results highlight the importance of taking into account physico-chemical properties of drugs and ligands when developing gold-based nanosystems, especially in the case of hydrophobic drugs

RELATIONSHIP BETWEEN COPING STRATEGIES AND EMOTIONAL INTELLIGENCE AMONG PATIENTS WITH SCHIZOPHRENIA

Background: Behavioural investigation has become increasingly more focused on emotional intelligence as researchers strive to understand its influence on various social interactions. Recent research indicates that EI plays an integral role in adopting active and effective coping strategies. The aim of this study was to investigate the relationship between emotional intelligence and coping strategies in patients with schizophrenia. Subjects and methods: The research included 102 stable patients with ICD-10 diagnosis of schizophrenia. The sample consisted of 46 (45.1%) female and 56 (54.9%) male patients, in the 18-55 age range (M=35.54; sd=10.48). All the participants completed the Questionnaire of Emotional Intelligence and Competence (UEK-45) and the Coping Inventory for Stressful Situations (CISS). Results: Data were analysed using the correlation coefficient and linear regression analysis. The results showed that emotional intelligence correlates significantly with both task-oriented and avoidance-oriented strategies (including social diversion and distraction). Regression analysis revealed that emotional intelligence can be a significant predictor for these two coping strategies (task-oriented and avoidance-oriented strategies (including social diversion and distraction)). Conclusion: Patients with lower emotional intelligence mainly use strategies focused on coping with their own emotions. These results may prompt the devising of prevention and treatment programs for patients suffering from schizophrenia. Namely, numerous studies and research on emotional intelligence show that emotional intelligence can be enhanced through learning and behaviour modification at any age

Harnessing adaptive novelty for automated generation of cancer treatments

© 2020 The Authors Nanoparticles have the potential to modulate both the pharmacokinetic and pharmacodynamic profiles of drugs, thereby enhancing their therapeutic effect. The versatility of nanoparticles allows for a wide range of customization possibilities. However, it also leads to a rich design space which is difficult to investigate and optimize. An additional problem emerges when they are applied to cancer treatment. A heterogeneous and highly adaptable tumour can quickly become resistant to primary therapy, making it inefficient. To automate the design of potential therapies for such complex cases, we propose a computational model for fast, novelty-based machine learning exploration of the nanoparticle design space. In this paper, we present an evolvable, open-ended agent-based model, where the exploration of an initially small portion of the given state space can be expanded by an ongoing generation of adaptive novelties, whenever the simulated tumour makes an adaptive leap. We demonstrate that the nano-agents can continuously reshape themselves and create a heterogeneous population of specialized groups of individuals optimized for tracking and killing different phenotypes of cancer cells. In the conclusion, we outline further development steps so this model could be used in real-world research and clinical practice

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2−. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans

pH-Responsive Hydrogel Beads Based on Alginate, k-Carrageenan and Poloxamer for enhanced curcumin, natural bioactive compound, encapsulation and controlled release efficiency

Polyphenolic compounds are used for treating various diseases due to their antioxidant and anticancer properties. However, utilization of hydrophobic compounds is limited due to their low bioavailability. In order to achieve a greater application of hydrophobic bioactive compounds, hydrogel beads based on biopolymers can be used as carriers for their enhanced incorporation and controlled delivery. In this study, beads based on the biopolymers-k-carrageenan, sodium alginate and poloxamer 407 were prepared for encapsulation of curcumin. The prepared beads were characterized using IR, SEM, TGA and DSC. The curcumin encapsulation efficiency in the developed beads was 95.74 +/- 2.24%. The release kinetics of the curcumin was monitored in systems that simulate the oral delivery (pH 1.2 and 7.4) of curcumin. The drug release profiles of the prepared beads with curcumin indicated that the curcumin release was significantly increased compared with the dissolution of curcumin itself. The cumulative release of curcumin from the beads was achieved within 24 h, with a final release rate of 12.07% (gastric fluid) as well as 81.93% (intestinal fluid). Both the in vitro and in vivo studies showed that new hydrogel beads based on carbohydrates and poloxamer improved curcumin’s bioavailability, and they can be used as powerful carriers for the oral delivery of different hydrophobic nutraceuticals

Evolutionary computational platform for the automatic discovery of nanocarriers for cancer treatment

We present the EVONANO platform for the evolution of nanomedicines with application to anti-cancer treatments. Our work aims to decrease both the time and cost required to develop nanoparticle designs. EVONANO includes a simulator to grow tumours, extract representative scenarios, and simulate nanoparticle transport through these scenarios in order to predict nanoparticle distribution. The nanoparticle designs are optimised using machine learning to efficiently find the most effective anti-cancer treatments. We demonstrate EVONANO with two examples optimising the properties of nanoparticles and treatment to selectively kill cancer cells over a range of tumour environments. Our platform shows how in silico models that capture both tumour and tissue-scale dynamics can be combined with machine learning to optimise nanomedicine

Curcumin and diclofenac therapeutic efficacy enhancement applying transdermal hydrogel polymer films, based on carrageenan, alginate and poloxamer

Films based on carrageenan, alginate and poloxamer 407 have been formulated with the main aim to apply prepared formulations in wound healing process. The formulated films were loaded with diclofenac, an anti-inflammatory drug, as well as diclofenac and curcumin, as multipurpose drug, in order to enhance encapsulation and achieve controlled release of these low bioavailable compounds. The obtained data demonstrated improved drugs bioavailability (encapsulation efficiency higher than 90%), with achieved high, cumulative in vitro release percentages (90.10% for diclofenac; 89.85% for curcumin and 95.61% for diclofenac in mixture-incorporated films).. The results obtained using theoretical models suggested that curcumin establish stronger, primarily dispersion interactions with carrier, in comparison with diclofenac. Curcumin and diclofenac-loaded films showed a great antibacterial activity against Gram-positive bacteria strains (Bacillus subtilis and Staphylococcus aureus, inhibition zone 16.67 mm and 13.67 mm, respectively), and in vitro and in vivo studies indicated that curcumin- and diclofenac-incorporated polymer films have a great tendency, as a new transdermal dressing, to heal wounds, because diclofenac can target the inflammatory phase and reduce pain, whereas curcumin can enhance and promote wound healing process

Technostress and academic motivation: direct and indirect effects on university students' psychological health

Introduction: Research has well demonstrated that the pandemic entailed several implications among university students worldwide in terms of increased use of Information and Communication Technologies (ICTs), technostress, disruptions in academic goals and motivation processes, and growing psychological suffering. Responding to the new research need to go in-depth into the processes linking technostress and motivation dimensions to inform current research/interventions, the present study aimed to explore the direct effects of perceived Technostress dimensions (Techno-Overload, Work-Home Conflict, Pace of Change, Techno-Ease, Techno-Reliability, and Techno-Sociality) and Academic Motivation dimensions (Amotivation, Intrinsic, and Extrinsic Motivation dimensions) on students' perceived levels of Anxiety/Depression and test the potential indirect effect (mediating role) of Academic Motivation dimensions in the associations between Technostress and psychological health conditions. Methods: Overall, 1,541 students from five European countries (Czech Republic, Greece, Italy, Serbia, United Kingdom) completed a survey comprising a Background Information Form, the Technostress Scale, the Academic Motivation Scale-College, and the Hospital Anxiety and Depression Scale. Hayes' PROCESS tool was used to test direct and indirect (mediating) effects. Results: Data revealed that Techno-Overload, Work-Home Conflict, Amotivation, and Extrinsic Motivation-Introjected had a direct negative effect, whereas Techno-Ease, Techno-Reliability, Techno-Sociality, all Intrinsic Motivation dimensions, and Extrinsic Motivation-Identified had a direct protective role for students' psychological health. The significant indirect role of motivation dimensions in the associations between Technostress dimensions and Anxiety/Depression was fully supported. Discussion: Findings allow gaining further insight into the pathways of relationships between technostress, motivation, and psychological health, to be used in the current phase, featured by the complete restoration of face-to-face contacts, to inform the development of tailored research and interventions, which address lights and shadows of the technology use, and which take into account the necessity to enhance its potentials yet without impairing students' motivation and psychological health

IL-33 Prevents MLD-STZ Induction of Diabetes and Attenuate Insulitis in Prediabetic NOD Mice

Type 1 diabetes is an autoimmune disease caused by the immune-mediated destruction of pancreatic β-cells. Prevention of type 1 diabetes requires early intervention in the autoimmune process against beta-cells of the pancreatic islets of Langerhans, which is believed to result from disordered immunoregulation. CD4+Foxp3+ regulatory T cells (Tregs) participate as one of the most important cell types in limiting the autoimmune process. The aim of this study was to investigate the effect of exogenous IL-33 in multiple low dose streptozotocin (MLD-STZ) induced diabetes and to delineate its role in the induction of protective Tregs in an autoimmune attack. C57BL/6 mice were treated i. p. with five doses of 40 mg/kg STZ and 0.4 μg rIL-33 four times, starting from day 0, 6, or 12 every second day from the day of disease induction. 16 weeks old NOD mice were treated with 6 injections of 0.4 μg/mouse IL-33 (every second day). Glycemia and glycosuria were measured and histological parameters in pancreatic islets were evaluated at the end of experiments. Cellular make up of the pancreatic lymph nodes and islets were evaluated by flow cytometry. IL-33 given simultaneously with the application of STZ completely prevented the development of hyperglycemia, glycosuria and profoundly attenuated mononuclear cell infiltration. IL-33 treatment was accompanied by higher number of IL-13 and IL-5 producing CD4+ T cells and increased presence of ST2+Foxp3+ regulatory T cells in pancreatic lymph nodes and islets. Elimination of Tregs abrogated protective effect of IL-33. We provide evidence that exogenous IL-33 completely prevents the development of T cell mediated inflammation in pancreatic islets and consecutive development of diabetes in C57BL/6 mice by facilitating the induction Treg cells. To extend this finding for possible relevance in spontaneous diabetes, we showed that IL-33 attenuate insulitis in prediabetic NOD mice