Redox Balance and Inflammatory Response in Follicular Fluids of Women Recovered by SARS-CoV-2 Infection or Anti-COVID-19 Vaccinated: A Combined Metabolomics and Biochemical Study.

To date, not many studies have presented evidence of SARS-CoV-2 infecting the female reproductive system. Furthermore, so far, no effect of the administration of anti-COVID 19 vaccines has been reported to affect the quality of oocytes retrieved from women who resorted to assisted reproduction technology (ART). The FF metabolic profiles of women who had been infected by SARS-CoV-2 before IVF treatments or after COVID-19 vaccination were examined by 1H NMR. Immunochemical characterization of proteins and cytokines involved in the redox and inflammatory pathways was performed. The increased expression of SOD2 and NQO1, the lack of alteration of IL-6 and CXCL10 levels, as well as the increased expression of CD39, suggested that, both sharing similar molecular mechanisms or proceeding along different routes, the redox balance is controlled in the FF of both vaccinated and recovered women compared to controls. The lower amount of metabolites known to have proinflammatory activity, i.e., TMAO and lipids, further supported the biochemical results, suggesting that the FF microenvironment is controlled so as to guarantee oocyte quality and does not compromise the outcome of ART. In terms of the number of blastocysts obtained after ICSI and the pregnancy rate, the results are also comforting.

The 75-99 C-Terminal Peptide of URG7 Protein Promotes α-Synuclein Disaggregation.

Up Regulation Gene seven (URG7) is the pseudogene 2 of the transporter ABCC6. The translated URG7 protein is localized with its single transmembrane α-helix in the endoplasmic reticulum (ER) membrane, orienting the N- and C-terminal regions in the lumen and cytoplasm, respectively, and it plays a crucial role in the folding of ER proteins. Previously, the C-terminal region of URG7 (PU, residues 75-99) has been shown to modify the aggregation state of α-synuclein in the lysate of HepG2 cells. PU analogs were synthesized, and their anti-aggregation potential was tested in vitro on α-synuclein obtained using recombinant DNA technology. Circular dichroism (CD), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and microscopic techniques were used to assess the sample's behavior. The results show that the peptides studied by themselves are prone to clathrate-like structure formation of variable stability. Aggregation of α-synuclein is accompanied by desolvation of its peptide chain and an increase in intermolecular ß-sheets. The PU analogs all interact with α-synuclein aggregates and those possessing the most stable clathrate-like structures have the highest disaggregating effect. These findings suggest that the C-terminal region of URG7 may have a role in interacting and modulating α-synuclein structures and could be used to generate interesting therapeutic candidates as disaggregators of α-synuclein.

Polyurethane Foams Loaded with Carbon Nanofibers for Oil Spill Recovery: Mechanical Properties under Fatigue Conditions and Selective Absorption in Oil/Water Mixtures.

Marine pollution due to spillage of hydrocarbons represents a well-known current environmental problem. In order to recover the otherwise wasted oils and to prevent pollution damage, polyurethane foams are considered suitable materials for their ability to separate oils from sea-water and for their reusability. In this work we studied polyurethane foams filled with carbon nanofibers, in varying amounts, aimed at enhancing the selectivity of the material towards the oils and at improving the mechanical durability of the foam. Polyurethane-based foams were experimentally characterized by morphological, surface, and mechanical analyses (optical microscopy observation, contact angle measurement, absorption test according to ASTM F726-99 standard and compression fatigue tests according to ISO 24999 standard). Results indicated an increase in hydrophobic behavior and a good oleophilic character of the composite sponges besides an improved selective absorption of the foam toward oils in mixed water/oil media. The optimal filler amount was found to be around 1 wt% for the homogeneous distribution inside the polymeric foam. Finally, the fatigue test results showed an improvement of the mechanical properties of the foam with the growing carbon filler amount.

A Smart Nanovector for Cancer Targeted Drug Delivery Based on Graphene Quantum Dots.

Graphene quantum dots (GQD), the new generation members of graphene-family, have shown promising applications in anticancer therapy. In this study, we report the synthesis of a fluorescent and biocompatible nanovector, based on GQD, for the targeted delivery of an anticancer drug with benzofuran structure (BFG) and bearing the targeting ligand riboflavin (RF, vitamin B2). The highly water-dispersible nanoparticles, synthesized from multi-walled carbon nanotubes (MWCNT) by prolonged acidic treatment, were linked covalently to the drug by means of a cleavable PEG linker while the targeting ligand RF was conjugated to the GQD by π⁻π interaction using a pyrene linker. The cytotoxic effect of the synthesized drug delivery system (DDS) GQD-PEG-BFG@Pyr-RF was tested on three cancer cell lines and this effect was compared with that exerted by the same nanovector lacking the RF ligand (GQD-PEG-BFG) or the anticancer drug (GQD@Pyr-RF). The results of biological tests underlined the low cytotoxicity of the GQD sample and the cytotoxic activity of the DDS against the investigated cancer cell lines with a higher or similar potency to that exerted by the BFG alone, thus opening new possibilities for the use of this drug or other anticancer agents endowed of cytotoxicity and serious side effects.

Graphene Quantum Dots Based Systems As HIV Inhibitors.

Graphene quantum dots (GQD) are the next generation of nanomaterials with great potential in drug delivery and target-specific HIV inhibition. In this study we investigated the antiviral activity of graphene based nanomaterials by using water-soluble GQD synthesized from multiwalled carbon nanotubes (MWCNT) through prolonged acidic oxidation and exfoliation and compared their anti-HIV activity with that exerted by reverse transcriptase inhibitors (RTI) conjugated with the same nanomaterial. The antiretroviral agents chosen in this study, CHI499 and CDF119, belong to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI). From this study emerged the RTI-conjugated compound GQD-CHI499 as a good potential candidate for HIV treatment, showing an IC50 of 0.09 µg/mL and an EC50 value in cell of 0.066 µg/mL. The target of action in the replicative cycle of HIV of the drug conjugated samples GQD-CHI499 and GQD-CDF119 was also investigated by a time of addition (TOA) method, showing for both conjugated samples a mechanism of action similar to that exerted by NNRTI drugs.

In vitro assessment of neurotoxicity and neuroinflammation of homemade MWCNTs.

Multi walled carbon nanotubes (MWCNTs) activate pathways involved in cytotoxicity, genotoxicity and inflammation. Inhaled MWCNTs are translocated to extra pulmonary organs and their hydrophobicity allows them to cross the blood-brain barrier (BBB). Further exposure of central nervous system (CNS) occurs via olfactory neurons. Using differentiated SH-SY5Y, we studied the neurotoxicity and neuroinflammation of pristine and functionalised MWCNTs. ROS overproduction was dose- and time-dependent (P<0.01) and was related to mitochondrial impairment, DNA damage and decreased viability (P<0.05). Transcript levels of TNFα, IL-1ß and IL-6 increased, as confirmed by an ELISA test. Raman spectra were acquired to assess MWCNT-cells interactions. The almost superimposable pro-oxidant activity of both CNTs could be imputable to excessive lengths with regard to the pristine MWCNTs and to the eroded surface, causing increased reactivity, with regard to functionalised MWCNTs. Considering the ease with which lightweight MWCNTs aerosolize and the increased production, the results underlined the potential onset of neurodegenerative diseases, due to unintentional MWCNT exposure.

The role of the iron catalyst in the toxicity of multi-walled carbon nanotubes (MWCNTs).

This study aimed to investigate the role of iron, used as a catalyst, in the biological response to pristine and functionalized multi-walled carbon nanotubes (p/fMWCNTs) with an iron content of 2.5-2.8%. Preliminarily, we assessed the pro-oxidant activity of MWCNTs-associated iron by an abiotic test. To evaluate iron bioavailability, we measured intracellular redox-active iron in A549 cells exposed to both MWCNT suspensions and to the cell medium preconditioned by MWCNTs, in order to assess the iron dissolution rate under physiological conditions. Moreover, in exposed cells, we detected ROS levels, 8-oxo-dG and mitochondrial function. The results clearly highlighted that MWCNTs- associated iron was not redox-active and that iron leakage did not occur under physiological conditions, including the oxidative burst of specialized cells. Despite this, in MWCNTs exposed cells, higher level of intracellular redox-active iron was measured in comparison to control and a significant time-dependent ROS increase was observed (P<0.01). Higher levels of 8-oxo-dG, a marker of oxidative DNA damage, and decreased mitochondrial function, confirmed the oxidative stress induced by MWCNTs. Based on the results we believe that oxidative damage could be attributable to the release of endogenous redox-active iron. This was due to the damage of acidic vacuolar compartment caused by endocytosis-mediated MWCNT internalization.

Graphene quantum dots for cancer targeted drug delivery.

A biocompatible and cell traceable drug delivery system Graphene Quantum Dots (GQD) based, for the targeted delivery of the DNA intercalating drug doxorubicin (DOX) to cancer cells, is here reported. Highly dispersible and water soluble GQD, synthesized by acidic oxidation and exfoliation of multi-walled carbon nanotubes (MWCNT), were covalently linked to the tumor targeting module biotin (BTN), able to efficiently recognize biotin receptors over-expressed on cancer cells and loaded with DOX. Biological test performed on A549 cells reported a very low toxicity of the synthesized carrier (GQD and GQD-BTN). In GQD-BTN-DOX treated cancer cells, the cytotoxicity was strongly dependent from cell uptake which was greater and delayed after treatment with GQD-BTN-DOX system with respect to what observed for cells treated with the same system lacking of the targeting module BTN (GQD-DOX) or with the free drug alone. A delayed nuclear internalization of the drug is reported, due to the drug detachment from the nanosystem, triggered by the acidic environment of cancer cells.

Graphene quantum dots: multifunctional nanoplatforms for anticancer therapy.

Graphene quantum dots, the next generation carbon based nanomaterials, due to their outstanding physical, chemical and biological properties, have shown potential in revolutionizing the future of nanomedicine and biotechnology. Their strong size-dependent photoluminescence (PL) and the presence of reactive groups on the GQD surface, which allow their multimodal conjugation with various functional groups and biologically active molecules, make them ideal candidates for cancer diagnosis and treatment. GQDs have been loaded with drugs and labeled with tumor-targeting ligand units that are able to specifically recognize cancer receptors exposed on the cancer cell surface by generating new therapies that are able to allow a more efficient targeted delivery of anticancer agents while minimizing their distribution in healthy tissues, as well as the development of new imaging agents for the in vitro and in vivo diagnosis of several types of cancer. Here, we review the recent advances in the study of the application of GQDs as nanoplatforms for anticancer therapy, taking into account the methods used for their synthesis and functionalization procedures, which can deeply affect their biocompatibility and their electronic and optical features. The biosafety and toxicity aspects of these nanomaterials at cellular and animal levels, mainly related to their size and the kind and degree of surface functionalization, are also discussed.

Tunable doxorubicin release from polymer-gated multiwalled carbon nanotubes.

Two pH and temperature controlled drug delivery systems for cancer therapy are here reported by using vapour phase and liquid phase functionalized multiwalled carbon nanotubes (MWCNT). Both oxidized MWCNT were functionalized at the carboxyl groups with a short hydrophilic polyethylene glycol (PEG) chain. The nanosystems were loaded with doxorubicin and covered with the biocompatible polymer polylactide, able to form hydrogen bonding with PEG and to entrape the drug inside the two polymeric chains. The different oxidative reaction conditions of MWCNT have demonstrated to deeply affect their agglomeration ability and the available reactive surface area for drug loading which in turn, affected the drug release abilities of the synthesized polymer-gated drug delivery systems. The in vitro release abilities as well as their antiproliferative effect on three different human cancer cell lines were evaluated and compared, highlighting the possibility to tune the amount of drug released by controlling the functionalization degree of the carbon nanotube based material. Biological tests highlighted the high biocompatibility of both systems and their ability to deliver doxorubicin to cancer cells.

Toxicological assessment of multi-walled carbon nanotubes on A549 human lung epithelial cells.

An in vitro model resembling the respiratory epithelium was used to investigate the biological response to laboratory-made pristine and functionalised multi-walled carbon nanotubes (pMWCNT and MWCNT-COOH). Cell uptake was analysed by MWCNT-COOH, FITC labelled and the effect of internalisation was evaluated on the endocytic apparatus, mitochondrial compartment and DNA integrity. In the dose range 12.5-100µgml(-1), cytotoxicity and ROS generation were assayed, evaluating the role of iron (the catalyst used in MWCNTs synthesis). We observed a correlation between MWCNTs uptake and lysosomal dysfunction and an inverse relationship between these two parameters and cell viability (P<0.01). In particular, pristine-MWCNT caused a time- and dose-dependent ROS increase and higher levels of lipid hydroperoxides compared to the controls. Mitochondrial impairment was observed. Conversely to the functionalised MWCNT, higher micronuclei (MNi) frequency was detected in mono- and binucleate pMWCNT-treated cells, underlining an aneugenic effect due to mechanical damage. Based on the physical and chemical features of MWCNTs, several toxicological pathways could be activated in respiratory epithelium upon their inhalation. The biological impacts of nano-needles were imputable to their efficient and very fast uptake and to the resulting mechanical damages in cell compartments. Lysosomal dysfunction was able to trigger further toxic effects.

Recent advances in carbon nanotubes as delivery systems for anticancer drugs.

Problems associated with the administration of anticancer drugs, such as limited solubility, poor biodistribution,lack of selectivity, and healthy tissue damage, can be overcome by the implementation of drug delivery systems. A wide range of materials, including liposomes, microspheres, polymers and recently, carbon nanotubes (CNTs), have been investigated for delivering anticancer drugs on the purpose of reducing the number of necessary administrations, providing more localized and better use of the active agents, and increasing patient compliance. Carbon nanotubes (CNTs) have attracted particular attention as carriers of biologically relevant molecules due to their unique physical, chemical and physiological properties. The exact relationship between the physical-chemical properties of carbon nanotubes, their cell to-cell interactions, reactivity, and biological/systemic consequences are relevant issues and it is important to know suchinter-relationships beforehand to employ the benefits of these nanomaterials without the hazardous consequences. The purpose of this review is to present highlight of recent developments in the application of carbon nanotubes as cargoes for anti cancer drugs and in the diagnosis of cancer diseases.