Innovative Low-Cost Composite Nanoadsorbents Based on Eggshell Waste for Nickel Removal from Aqueous Media.

In a contemporary sustainable economy, innovation is a prerequisite to recycling waste into new efficient materials designed to minimize pollution and conserve non-renewable natural resources. Using an innovative approach to remediating metal-polluted water, in this study, eggshell waste was used to prepare two new low-cost nanoadsorbents for the retrieval of nickel from aqueous solutions. Scanning electron microscopy (SEM) results show that in the first eggshell-zeolite (EZ) adsorbent, the zeolite nanoparticles were loaded in the eggshell pores. The preparation for the second (iron(III) oxide-hydroxide)-eggshell-zeolite (FEZ) nanoadsorbent led to double functionalization of the eggshell base with the zeolite nanoparticles, upon simultaneous loading of the pores of the eggshell and zeolite surface with FeOOH particles. Structural modification of the eggshell led to a significant increase in the specific surface, as confirmed using BET analysis. These features enabled the composite EZ and FEZ to remove nickel from aqueous solutions with high performance and adsorption capacities of 321.1 mg/g and 287.9 mg/g, respectively. The results indicate that nickel adsorption on EZ and FEZ is a multimolecular layer, spontaneous, and endothermic process. Concomitantly, the desorption results reflect the high reusability of these two nanomaterials, collectively suggesting the use of waste in the design of new, low-cost, and highly efficient composite nanoadsorbents for environmental bioremediation.

Unraveling the blood transcriptome after real-life exposure of Wistar-rats to PM2.5, PM1 and water-soluble metals in the ambient air.

Exposure to particulate matter (PM) is one of the most important environmental issues in Europe with major health impact. Various sizes of PM are suspended in the atmosphere and contributes to ambient air pollution. The current study aimed to explore the differential gene expression in blood, and the effect on the respective biological signaling pathways in Wistar rats, after exposure to PM2.5 and PM1 ambient air particles for an eight-week period. A control group was included with animals breathing non-filtered atmospheric air. In parallel, filtered PM2.5 and PM1 was collected in separate samplers. The results after whole genome microarray analysis showed 23 differentially expressed genes (DEGs) between control and PM2.5 group. In addition, pairwise comparison between control and PM1 group displayed 5635 DEGs linked to 69 biological pathways involved in inflammatory response, cell cycle and carcinogenicity. The smaller the size of the inhaled particles, the more gene alterations are triggered compared to non-filtered air group. More specifically, in inflammation signaling procedures differentially regulated gene expression was shown for interleukin-4 (IL-4), IL-7, IL-1, IL-5, IL-9, IL-6 and IL-2. We have identified that RASGFR1, TRIM65, TRIM33, PLEKHB1, CAR4, S100A8, S100A9, ALPL, NP4 and the PROK2 genes are potential targets for the development of adverse outcome pathways (AOPs) due to "real-life" exposure of Wistar rats. Particle measurements during the exposure period showed elevated concentrations of Fe, Mn and Zn in both PM1 and PM2.5 filter fractions, and of Cu in PM2.5. In addition, water-soluble concentration of metals showed significant differences between PM1 and PM2.5 fractions for V, Zn, As, Pb and Mn. In summary, in this study specific gene biomarkers of exposure to ambient air have been identified and heavy metals that are possibly linked to their altered regulation have been found. The results of this research will pave the way for the development of novel AOPs concerning the health effects of the environmental pollution.

Magnetic cationic liposomal nanocarriers for the efficient drug delivery of a curcumin-based vanadium complex with anticancer potential.

In this work novel magnetic cationic liposomal nanoformulations were synthesized for the encapsulation of a crystallographically defined ternary V(IV)-curcumin-bipyridine (VCur) complex with proven bioactivity, as potential anticancer agents. The liposomal vesicles were produced via the thin film hydration method employing N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium (DOTAP) and egg phosphatidylcholine lipids and were magnetized through the addition of citric acid surface-modified monodispersed magnetite colloidal magnetic nanoparticles. The obtained nanoformulations were evaluated for their structural and textural properties and shown to have exceptional stability and enhanced solubility in physiological media, demonstrated by the entrapment efficiency and loading capacity results and the in vitro release studies of their cargo. Furthermore, the generated liposomal formulations preserved the superparamagnetic behavior of the employed magnetic core maintaining the physicochemical and morphological requirements for targeted drug delivery applications. The novel nanomaterials were further biologically evaluated for their DNA interaction potential and were found to act as intercalators. The findings suggest that the positively charged magnetic liposomal nanoformulations can generate increased concentration of their cargo at the DNA site, offering a further dimension in the importance of cationic liposomes as nanocarriers of hydrophobic anticancer metal ion complexes for the development of new multifunctional pharmaceutical nanomaterials with enhanced bioavailability and targeted antitumor activity.

Metallodrugs in Targeted Cancer Therapeutics: Aiming at Chemoresistance- related Patterns and Immunosuppressive Tumor Networks.

Tumor cell chemoresistance is a major challenge in cancer therapeutics. Major select metal-based drugs are potent anticancer mediators yet they exhibit adverse sideeffects and are efficient against limited types of malignancies. A need, therefore, arises for novel metallodrugs with improved efficacy and decreased toxicity. Enhancement of antitumor drugs based on anticancer metals is currently a very active research field, with considerable efforts having been made toward elucidating the mechanisms of immune action of complex metalloforms and optimizing their immunoregulatory bioactivity through appropriate synthetic structural modification(s) and encapsulation in suitable nanocarriers, thereby enhancing their selectivity, specificity, stability, and bioactivity. In that respect, comprehending the molecular factors involved in drug resistance and immune response may help us develop new approaches toward more promising chemotherapies, reducing the rate of relapse and overcoming chemoresistance. In this review, a) molecular immunerelated mechanisms in the tumor microenvironment, responsible for lower drug sensitivity and tumor relapse, along with b) strategies for reversing drug resistance and targeting immunosuppressive tumor networks, while concurrently optimizing the design of complex metalloforms bearing anti-tumor activity, are discussed in an effort to identify and overcome chemoresistance mechanisms for effective tumor immunotherapeutic approaches.

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.

In vitro and ex vivo vanadium antitumor activity in (TGF-ß)-induced EMT. Synergistic activity with carboplatin and correlation with tumor metastasis in cancer patients.

Epithelial to mesenchymal transition (EMT) plays a key role in tumor progression and metastasis as a crucial event for cancer cells to trigger the metastatic niche. Transforming growth factor-ß (TGF-ß) has been shown to play an important role as an EMT inducer in various stages of carcinogenesis. Previous reports had shown that antitumor vanadium inhibits the metastatic potential of tumor cells by reducing MMP-2 expression and inducing ROS-dependent apoptosis. However, the role of vanadium in (TGF-ß)-induced EMT remains unclear. In the present study, we report for the first time on the inhibitory effects of vanadium on (TGF-ß)-mediated EMT followed by down-regulation of ex vivo cancer stem cell markers. The results demonstrate blockage of (TGF-ß)-mediated EMT by vanadium and reduction in the mitochondrial potential of tumor cells linked to EMT and cancer metabolism. Furthermore, combination of vanadium and carboplatin (a) resulted in synergistic antitumor activity in ex vivo cell cultures, and (b) prompted G0/G1 cell cycle arrest and sensitization of tumor cells to carboplatin-induced apoptosis. Overall, the findings highlight the multifaceted antitumor action of vanadium and its synergistic antitumor efficacy with current chemotherapy drugs, knowledge that could be valuable for targeting cancer cell metabolism and cancer stem cell-mediated metastasis in aggressive chemoresistant tumors.

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.

Differential expression of IL-17, 22 and 23 in the progression of colorectal cancer in patients with K-ras mutation: Ras signal inhibition and crosstalk with GM-CSF and IFN-γ.

Recent studies have suggested that aberrant K-ras signaling is responsible for triggering immunological responses and inflammation-driven tumorigenesis. Interleukins IL-17, IL-22, and IL-23 have been reported in various types of malignancies, but the exact mechanistic role of these molecules remains to be elucidated. Given the role of K-ras and the involvement of interleukins in colorectal tumorigenesis, research efforts are reported for the first time, showing that differentially expressed interleukin IL-17, IL-22, and IL-23 levels are associated with K-ras in a stage-specific fashion along colorectal cancer progression. Specifically, a) the effect of K-ras signaling was investigated in the overall expression of interleukins in patients with colorectal cancer and healthy controls, and b) an association was established between mutant K-ras and cytokines GM-CSF and IFN-γ. The results indicate that specific interleukins are differentially expressed in K-ras positive patients and the use of K-ras inhibitor Manumycin A decreases both interleukin levels and apoptosis in Caco-2 cells by inhibiting cell viability. Finally, inflammation-driven GM-CSF and IFN-γ levels are modulated through interleukin expression in tumor patients, with interleukin expression in the intestinal lumen and cancerous tissue mediated by aberrant K-ras signaling. Collectively, the findings a) indicate that interleukin expression is influenced by ras signaling and specific interleukins play an oncogenic promoter role in colorectal cancer, highlighting the molecular link between inflammation and tumorigenesis, and b) accentuate the interwoven molecular correlations as leads to new therapeutic approaches in the future.

Novel ternary vanadium-betaine-peroxido species suppresses H-ras and matrix metalloproteinase-2 expression by increasing reactive oxygen species-mediated apoptosis in cancer cells.

Vanadium is known for its antitumorigenicity. Poised to investigate the impact of well-defined forms of vanadium on processes and specific biomolecules (oncogenes-proteins) involved in cancer cell physiology, a novel ternary V(V)-peroxido-betaine compound was employed in experiments targeting cell viability, apoptosis, reactive oxygen species (ROS) production, H-ras signaling, and matrix metalloproteinase-2 (MMP-2) expression in human breast cancer epithelial and lung adenocarcinoma cells. The results reveal that vanadium imparts a significant decrease in cancer cell viability, reducing H-ras and MMP-2 expression by increasing ROS-mediated apoptosis, distinctly emphasizing the nature, structure and properties of ternary ligands on vanadium anti-tumor activity and its future potential as a metallodrug.

Cadmium modulates H-ras expression and caspase-3 apoptotic cell death in breast cancer epithelial MCF-7 cells.

Cadmium (Cd) is a well-known metal carcinogen associated with tumor formation and carcinogenesis. It has been shown to induce cancer through various cellular mechanisms involving inhibition of DNA repair, abnormal gene expression, induction of oxidative stress, and triggering apoptosis. It is well-established that the H-ras oncogene is involved in the process of carcinogenesis with direct effects on cellular proliferation and tumorigenesis. Given the biotoxicity of cadmium and its association with carcinogenesis, the effect of that metal ion (Cd(II)) was investigated, in a concentration-dependent fashion, on cell viability, cell proliferation, caspase-3 mediated apoptosis and H-ras gene expression in human breast cancer epithelial MCF-7 cells transfected with the H-ras oncogene (wild type and G12V mutation). The findings show a significant modulation effect of cadmium on H-ras gene expression accompanied by up-regulation of caspase-3-related apoptosis in the concentration range of 100-1000 nΜ cadmium. Concurrently, there is a decrease in MCF-7 proliferation. Collectively, the results a) indicate an interplay of cadmium with H-ras(wt and G12V), with cadmium exhibiting a significant concentration-dependent effect on the modulation of H-ras expression, cell viability and proliferation, and b) project distinctly interwoven roles for both cadmium and H-ras in aberrant physiologies in cancer cells.

Antioxidant activity of organic extracts from aqueous infusions of sage.

The antioxidant activity of aqueous infusions of sage emerges from specific components present in that herb. In an attempt to investigate the chemical nature and properties of these components, four organic solvent extracts from aqueous infusions of sage were examined. HPLC analyses of these extracts led to the separation of a number of components, of which four were identified and quantified through the use of standard compounds of known chromatographic HPLC profiles. These compounds are the diterpenes carnosic acid, carnosol, and rosmanol and the hydroxycinnamic acid caffeic acid. The antioxidant activity and polyphenol content were determined in the four organic solvent extracts and the left-over aqueous fraction. Both polyphenolic and nonpolyphenolic substances present in the extracts arise as significant contributors to the observed antioxidant activity of the derived extracts and thus sage itself. In this sense, they reflect the antioxidant potential of the aqueous infusions of sage toward reactive oxygen species generated through variable mechanisms of iron-promoted oxidative processes.

A novel dinuclear species in the aqueous distribution of aluminum in the presence of citrate.

The chemistry of aluminum was explored in the presence of the physiological ligand citric acid and in low-pH aqueous media. As a result, the first dinuclear aluminum-citrate complex (NH4)4[Al2-(C6H4O7)(C6H5O7)2].4H2O was isolated at low pH (approximately 3.5), and was characterized by FT-IR spectroscopy and X-ray crystallography. The structural analysis reveals the presence of a dinuclear assembly of two aluminum ions octahedrally coordinated to three citrate ligands of differing protonation state. The NMR solution behavior of this complex emphasizes its time-dependent transformation into a number of variable nature species, ultimately leading to the thermodynamically stable trinuclear species. It also establishes the participation of the dinuclear complex as a viable component of the aqueous Al(III)-citrate speciation. The chemical and structural features of this novel low molecular mass species provide considerable insight into citrate's ability, as a natural ligand, to influence the chemistry of aluminum in a pH-dependent fashion, and potentially affect aluminum's (bio)distribution, absorption, accumulation, and biotoxicity at sensitive biological sites.