C.M. Nday

Mechanisms and Αpplications of Ιnterleukins 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.

Quercetin encapsulation in modified silica nanoparticles: potential use against Cu(II)-induced oxidative stress in neurodegeneration.

Neurodegenerative diseases entail deeply complex processes, intimately associated with progressive brain damage reflecting cellular demise. Biochemical reactivity linked to such processes in Alzheimers disease involves, among others, metal-induced oxidative stress contributing to neuronal cell death. Prominent among redox active metals inducing oxidative stress is Cu(II). Poised to develop molecular technology counteracting oxidative stress, efforts were launched to prepare bioactive hybrid nanoparticles, capable of working as host-carriers of potent antioxidants, such as the natural flavonoid quercetin. Employing synthetic protocols consistent with the assembly of silica nanoparticles, PEGylated and CTAB-modified materials were synthesized. Subsequent concentration-dependent loading of quercetin led to well-defined molecular carriers, the antioxidant efficiency of which was determined through drug release studies using UV-visible spectroscopy. The physicochemical characterization (elemental analysis, particle size, z-potential, FT-IR, thermogravimetric analysis, scanning electron microscopy) of the empty and loaded silica nanoparticles led to the formulation of optimized material linked to the delivery of the encapsulated antioxidant to primary rat hippocampal cultures under oxidative stress. Entrapment and drug release studies showed a) the competence of hybrid nanoparticles as far as the loading capacity in quercetin (concentration dependence), b) congruence with the physicochemical features determined, and c) the release profile of the nanoparticle load under oxidative stress in neuronal cultures. The bio-activity profile of quercetin nanoparticles in a neurodegenerative environment brought on by Cu(II) a) denotes the improved specificity of antioxidant reactivity counteracting oxidative stress, and b) sets the stage for the development of molecular protection and preventive medical nanotechnology of relevance to neurodegenerative Alzheimers disease.

In vitro neurotoxic Fe(III) and Fe(III)-chelator activities in rat hippocampal cultures. From neurotoxicity to neuroprotection prospects

It is well known that iron dysregulation is involved in a number of processes involving genetic and non-genetic factors leading to neurodegeneration. Molecules bearing iron or influencing iron metabolism reflect directly into the levels of that redox active metal, present as Fe(II)/Fe(III), in the brain. In turn, iron level variations are associated with chemical reactivity disrupting iron homeostasis, generating variable neurotoxic iron forms and contributing to the vulnerability of cells toward oxidative stress and neuronal death in Alzheimers disease (AD). Efforts to delineate the interactions of neurotoxic Fe(III) with low molecular mass substrates, relevant to cellular processes, led to the discovery of specific well-defined binary iron-quinate (FeQ) species. Poised to investigate the specific effects of a) well-defined forms of labile soluble Fe(III), b) the nature and chemistry of the ligand bound to Fe(III), and c) a natural metal ion binder - quinic acid - acting as a potential neuroprotectant toward iron toxicity, FeCl(3), FeQ, and free quinate were employed in in vitro studies involving primary rat hippocampal cultures. Three hour and 24-hour exposures of such cultures to Fe(III) reveal significant differential effects on both glial and neuronal cell survival linked to neurotoxicity of the specific yet variably composed complex forms of iron. The use of quinic acid both in the free and bound form to Fe(III) a) exemplifies essential structural and chemical attributes of naturally encountered metal ion binders promoting well-defined interactions with neurotoxic Fe(III), and b) signifies the potential linkage of labile Fe(III) chemical reactivity in neurodegeneration with natural substrate neuroprotection.

Sol–gel encapsulation of binary Zn(II) compounds in silica nanoparticles. Structure–activity correlations in hybrid materials targeting Zn(II) antibacterial use

In the emerging issue of enhanced multi-resistant properties in infectious pathogens, new nanomaterials with optimally efficient antibacterial activity and lower toxicity than other species attract considerable research interest. In an effort to develop such efficient antibacterials, we a) synthesized acid-catalyzed silica-gel matrices, b) evaluated the suitability of these matrices as potential carrier materials for controlled release of ZnSO4 and a new Zn(II) binary complex with a suitably designed well-defined Schiff base, and c) investigated structural and textural properties of the nanomaterials. Physicochemical characterization of the (empty-loaded) silica-nanoparticles led to an optimized material configuration linked to the delivery of the encapsulated antibacterial zinc load. Entrapment and drug release studies showed the competence of hybrid nanoparticles with respect to the a) zinc loading capacity, b) congruence with zinc physicochemical attributes, and c) release profile of their zinc load. The material antimicrobial properties were demonstrated against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and negative (Escherichia coli, Pseudomonas aeruginosa, Xanthomonas campestris) bacteria using modified agar diffusion methods. ZnSO4 showed less extensive antimicrobial behavior compared to Zn(II)-Schiff, implying that the Zn(II)-bound ligand enhances zinc antimicrobial properties. All zinc-loaded nanoparticles were less antimicrobially active than zinc compounds alone, as encapsulation controls their release, thereby attenuating their antimicrobial activity. To this end, as the amount of loaded zinc increases, the antimicrobial behavior of the nano-agent improves. Collectively, for the first time, sol-gel zinc-loaded silica-nanoparticles were shown to exhibit well-defined antimicrobial activity, justifying due attention to further development of antibacterial nanotechnology.

Shared pathological pathways of Alzheimer's disease with specific comorbidities: current perspectives and interventions

Alzheimers disease (AD) belongs to one of the most multifactorial, complex and heterogeneous morbidity‐leading disorders. Despite the extensive research in the field, AD pathogenesis is still at some extend obscure. Mechanisms linking AD with certain comorbidities, namely diabetes mellitus, obesity and dyslipidemia, are increasingly gaining importance, mainly because of their potential role in promoting AD development and exacerbation. Their exact cognitive impairment trajectories, however, remain to be fully elucidated. The current review aims to offer a clear and comprehensive description of the state‐of‐the‐art approaches focused on generating in‐depth knowledge regarding the overlapping pathology of AD and its concomitant ailments. Thorough understanding of associated alterations on a number of molecular, metabolic and hormonal pathways, will contribute to the further development of novel and integrated theranostics, as well as targeted interventions that may be beneficial for individuals with age‐related cognitive decline.

Synthetic investigation, physicochemical characterization and antibacterial evaluation of ternary Bi(III) systems with hydroxycarboxylic acid and aromatic chelator substrates

Due to its physical and chemical properties, bismuth (Bi(III)) is widely used in the treatment of several gastrointestinal and skin diseases, and infections caused by bacteria. Herein, its known antimicrobial potential was taken into consideration in the synthesis of two new hybrid ternary materials of Bi(III) with the physiological α-hydroxycarboxylic glycolic acid and 1,10-phenanthroline (phen), [Bi2(C2H2O3)2(C2H3O3)(NO3)]n. nH2O (1) and [Bi(C12H8N2)(NO3)4](C10H8N4) (2), aiming at improving its antibacterial properties. Their physicochemical characterization was carried out through elemental analysis, FT-IR, atomic absorption spectroscopy, single crystal X-ray diffraction, thermogravimetric analysis (TGA), photoluminescence, and 13C MAS-NMR techniques. The antimicrobial activity of the title complexes was directly linked to Bi(III) coordination environment and the incipient aqueous chemistry. For their antibacterial assessment, minimum inhibitory concentration (MIC), zone of inhibition (ZOI), and bacteriostatic-bacteriocidal activity were determined in various Gram positive (Staphylococcus aureus, Bacillus subtilis and Bacillus cereus) and Gram negative (Escherichia coli and Xanthomonas campestris) bacterial cultures, in reference to a positive control (ampicillin), encompassing further comparisons with literature data. The findings reveal that the new hybrid bismuth materials have significant antimicrobial effects against the employed bacteria. Specifically, 2 exhibits better antimicrobial properties than free Bi(NO3)3 and phen. On the other hand, 1 is bacteriostatic toward four microorganisms except X. campestris, with 2 being bacteriocidal toward four microorganisms except B. cereus. Collectively, the new hybrid, well-defined, and two of the rarely crystallographically characterized Bi(III) materials a) exhibit properties reflecting their physicochemical nature and reactivity, and b) are expected to contribute to the development of efficient metallodrugs against drug-resistant bacterial infections.

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.

Hybrid catechin silica nanoparticle influence on Cu(II) toxicity and morphological lesions in primary neuronal cells

Morphological alterations compromising inter-neuronal connectivity may be directly linked to learning-memory deficits in Central Nervous System neurodegenerative processes. Cu(II)-mediated oxidative stress plays a pivotal role in regulating redox reactions generating reactive oxygen species (ROS) and reactive nitrogen species (RNS), known contributors to Alzheimers disease (AD) pathology. The antioxidant properties of flavonoid catechin have been well-documented in neurodegenerative processes. However, the impact that catechin encapsulation in nanoparticles may have on neuronal survival and morphological lesions has been poorly demonstrated. To investigate potential effects of nano-encapsulated catechin on neuronal survival and morphological aberrations in primary rat hippocampal neurons, poly(ethyleneglycol) (PEG) and cetyltrimethylammonium bromide (CTAB)-modified silica nanoparticles were synthesized. Catechin was loaded on silica nanoparticles in a concentration-dependent fashion, and release studies were carried out. Further physicochemical characterization of the new nano-materials included elemental analysis, particle size, z-potential, FT-IR, Brunauer-Emmett-Teller (BET), thermogravimetric (TGA), and scanning electron microscopy (SEM) analysis in order to optimize material composition linked to the delivery of loaded catechin in the hippocampal cellular milieu. The findings reveal that, under Cu(II)-induced oxidative stress, the loading ability of the PEGylated/CTAB silica nanoparticles was concentration-dependent, based on their catechin release profile. The overall bio-activity profile of the new hybrid nanoparticles a) denoted their enhanced protective activity against oxidative stress and hippocampal cell survival compared to previously reported quercetin, b) revealed that morphological lesions affecting neuronal integrity can be counterbalanced at high copper concentrations, and c) warrants in-depth perusal of molecular events underlying neuronal function and degeneration, collectively linked to preventive nanotechnology in neurodegeneration.