Human blood adenosine biomarkers and non-rapid eye movement sleep stage 3 (NREM3) cortical functional connectivity associations during a 30-day head-down-tilt bed rest analogue: Potential effectiveness of a reactive sledge jump as a countermeasure.

We investigated the alterations of sleep regulation and promotion biomarkers as adenosine through its enzymes total adenosine deaminase (tADA)/adenosine deaminase (ADA2) in a microgravity analogue environment of head-down-tilt bed rest and their association with brain connectivity networks during non-rapid eye movement sleep stage 3 (NREM3), as well as the effectiveness of the reactive sledge (RSL) jump countermeasure to promote sleep. A total of 23 healthy male volunteers were maintained in 6° head-down-tilt position for 30 days and assigned either to a control or to a RSL group. Blood collection and polysomnographic recordings were performed on data acquisition day 1, 14, 30 and -14, 21, respectively. Immunochemical techniques and network-based statistics were employed for adenosine enzymes and cortical connectivity estimation. Our findings indicate that human blood adenosine biomarkers as well as NREM3 cortical functional connectivity are impaired in simulated microgravity. RSL physical activity intervened in sleep quality via tADA/ADA2 fluctuations lack, minor cortical connectivity increases, and limited degree of node and resting-state networks. Statistically significant decreases in adenosine biomarkers and NREM3 functional connectivity involving regions (left superior temporal gyrus, right postcentral gyrus, precuneus, left middle frontal gyrus, left postcentral gyrus, left angular gyrus and precuneus) of the auditory, sensorimotor default-mode and executive networks highlight the sleep disturbances due to simulated microgravity and the sleep-promoting role of RSL countermeasure. The head-down-tilt environment led to sleep deterioration projected through NREM3 cortical brain connectivity or/and adenosine biomarkers shift. This decline was more pronounced in the absence of the RSL countermeasure, thereby highlighting its likely exploitation during space missions.

Naringin nanoparticles against neurodegenerative processes: A preliminary work.

It is well established that during Alzheimer disease (AD), gradual loss of neuronal networks occurs in the brain, consequently, affecting cognition and memory tasks of the patients. Among other causative factors, oxidative stress induces changes that are eventually accompanied by an irreversible disruption of synaptic connectivity and death of neurons. Moreover, aging and oxidative stress cause alterations to the blood brain barrier, leading to increased permeability, which are thought to further aggravate the underlying pathology. Up to date, no effective treatment is available to Alzheimer's disease patients. Lately, scientific efforts are focusing on exploiting the antioxidant properties that natural polyphenol agents such as flavonoids possess and their potential beneficial effect against neurodegenerative diseases. For that reason, the current investigation, aims at developing more effective flavonoid agents by encapsulating naringin into modified PEG 3000 Silica nanoparticles before its use at cellular level. Overall, our findings suggest an enhanced protective capacity of naringin pegylated nanoparticles against Aß amyloid linked oxidative stress mediated neurodegeneration in primary rat neuronal and glial hippocampal cultures for a certain incubation period. The functional biological reactivities of the novel flavonoid nanoparticles were in line with their physicochemical features and reflect the a) differential nature of the structural assemblies of the new nanoparticles, thereby distinguishing them from other polymeric and liposomal drug carriers, and b) significance and impact of PEG chemistry in the synthetic assembly of the nanocarriers. The ability of the employed nanoparticles to entrap a relatively high dose of otherwise insoluble drugs and their biological activity highlight their potential as brain targeting therapeutics.

Advanced network neuroscience approaches in sleep neurobiology on extreme environments.

In this paper we propose a novel methodology for investigating pathological sleep patterns through network neuroscience approaches. It consists of initial identification of statistically significant alterations in cortical functional connectivity patterns. The resulting sub-network is then analyzed by employing graph theory for estimating both global performance metrics (integration and specialization) as well as the significance of specific network nodes and their hierarchical organization. So, nodes with important role in network structure are recognized and their functionality is correlated with adenosine biomarker which is important in sleep regulation and promotion. The aforementioned pipeline is applied in a dataset of sleep data gathered during a microgravity simulation experiment. The analysis was performed on cortical resting-state networks involved in sleep physiology. It demonstrated the detrimental effects of microgravity which were more prominent for the group which did not perform reactive sledge jumps as a countermeasure.

Chitosan encapsulation of essential oil "cocktails" with well-defined binary Zn(II)-Schiff base species targeting antibacterial medicinal nanotechnology.

The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance.

Mechanisms and applications of interleukins in cancer immunotherapy.

Over the past years, advances in cancer immunotherapy have resulted in innovative and novel approaches in molecular cancer diagnostics and cancer therapeutic procedures. However, due to tumor heterogeneity and inter-tumoral discrepancy in tumor immunity, the clinical benefits are quite restricted. The goal of this review is to evaluate the major cytokines-interleukins involved in cancer immunotherapy and project their basic biochemical and clinical applications. Emphasis will be given to new cytokines in pre-clinical development, and potential directions for future investigation using cytokines. Furthermore, current interleukin-based approaches and clinical trial data from combination cancer immunotherapies will also be discussed. It appears that continuously increasing comprehension of cytokine-induced effects, cancer stemness, immunoediting, immune-surveillance as well as understanding of molecular interactions emerging in the tumor microenvironment and involving microRNAs, autophagy, epithelial-mesenchymal transition (EMT), inflammation, and DNA methylation processes may hold much promise in improving anti-tumor immunity. To this end, the emerging in-depth knowledge supports further studies on optimal synergistic combinations and additional adjuvant therapies to realize the full potential of cytokines as immunotherapeutic agents.

Aluminum does not enhance beta-amyloid toxicity in rat hippocampal cultures.

A number of environmental factors have been implicated in neurodegenerative disorders, including metallotoxins such as aluminum (Al). In the present study, the toxicity of Al-quinate (AlQ), a well-characterized Al complex, was investigated in primary rat hippocampal cultures in comparison to inorganic Al (Al-S). AlQ was significantly less toxic than Al-S during both short- (3h) and long-term (24h) incubations. The neuroprotective properties of quinic acid (which constitutes the quinate moiety of AlQ) against short-term incubations with Al-S were subsequently assessed, and the organic compound was found to provide full protection, comparable to synthetic metal chelating agents desferrioxamine and clioquinol. Finally, potential synergistic actions between Al (AlQ and Al-S) and beta-amyloid (Abeta) were investigated. Neither Al form appeared to enhance Abeta toxicity, in fact, AlQ significantly reduced Abeta toxicity. Collectively, this study highlights further the impact of structural features and physiological ligands of metal complexes on toxicity profiles, and reveals promising properties of quinic acid as a metal chelator. Despite previous reports suggesting synergistic toxicity between Al and Abeta, we could not identify such a mechanism in our investigation.