Publications

Abstract This work reports the development of a simple and rapid electrochemical immunosensor for the determination of breast cancer biomarker Cancer Antigen 15-3 (CA 15-3). Disposable and cost-effective chips, consisting of gold screen-printed electrodes (AuSPEs), were used to develop the portable electrochemical devices for monitoring the biomarker in point-of-care (PoC), under clinical context. The biosensor preparation consisted of two simple steps. First, a self-assembled monolayer (SAM) of mercaptosuccinic acid (MSA) was formed at the AuSPE surface. Then, the CA 15-3 antibody was covalently bound to the carboxylic groups standing at the electrode surface using EDC/NHS chemistry. The performance of the developed immunosensor was evaluated by assessing the sensor sensitivity, linear response interval, selectivity and detection limit (LOD). The developed immunosensor provided a wide linear concentration range (from 1.0 to 1000 U mL(-1)) and low detection levels were achieved (LOD of 0.95 U mL(-1)), enabling the sensitive detection of the cancer biomarker at clinically relevant levels, using square wave voltammetry (SWV) as electroanalytical technique. Moreover, selectivity studies performed against other cancer biomarkers (CA 125 and CA 19-9) revealed that the antibody has high selectivity for CA 15-3 antigen. The immunosensor was applied to the quantification of CA 15-3 in artificial serum samples with satisfactory results.

Abstract Augmenter of liver regeneration (ALR) is a critical multi-isoform protein with its longer isoform, located in the mitochondrial intermembrane space, being part of the mitochondrial disulfide relay system (DRS). Upregulation of ALR was observed in multiple forms of cancer, among them hepatocellular carcinoma (HCC). To shed light into ALR function in HCC, we used MitoBloCK-6 to pharmacologically inhibit ALR, resulting in profound mitochondrial impairment and cancer cell proliferation deficits. These effects were mostly reversed by supplementation with bioavailable hemin b, linking ALR function to mitochondrial iron homeostasis. Since many tumor cells are known for their increased iron demand and since increased iron levels in cancer are associated with poor clinical outcome, these results help to further advance the intricate relation between iron and mitochondrial homeostasis in liver cancer.</p>

Abstract In this work, we describe an innovative methodology based on combined surface plasmon resonance (SPR) and electrochemical responses (eSPR) in the same immunoassay for screening CA 15-3 cancer biomarker with high sensitivity (and selectivity), in a very simple, label-free, accurate, and fully automated manner. Detection was achieved by performing two simple steps. In the first step, direct SPR was used to monitor CA 15-3 interaction with surface immobilized antibody. Two linear response ranges were obtained and the detection limit achieved is poor (LOD of 21 U mL(-1)). However, in the second detection step, electrochemical measurements at the SPR gold surface were performed to measure the decrease of redox probe peak current upon antigen-antibody interaction, providing a suitable amplification strategy to lower detection levels of CA 15-3 (LOD of 0.0998 U mL(-1)), without the need of additional complex and/or expensive amplification steps to enhance the sensitivity. Moreover, selectivity studies were performed against other common cancer biomarkers and the results showed that the eSPR immunosensor is selective for the CA 15-3 protein. Finally, the clinical applicability of the developed eSPR biosensing methodology was successfully applied to detect CA 15-3 in human serum samples at clinically relevant levels due to the high sensitivity of electrochemical readout. The same concept may be further extended to other proteins of interest.

Abstract In this study, Co-TiO2 nanoparticles were successfully synthesized using sol-gel and precipitation methods. The effect of Co amount on the physicochemical properties of these nanomaterials was investigated using various techniques. The obtained results showed that the structural and optical properties of the synthesized Co-TiO2 nanomaterials depended closely on the weight percent of Co added to TiO2. It was found that, for 1%Co-TiO2, a substitution of Ti4+ and Co2+/Co3+ within the lattice of TiO2 was happened. The results of the photocatalytic degradation of methyl orange (MO) experiments carried out in the presence of the as prepared nanomaterials showed that under visible light, the sample 1%Co-TiO2 exhibited the best MO conversion. The enhanced photocatalytic activity has been attributed to the efficient charge separation of electrons and holes. The mechanistic studies revealed that O-2(center dot-), h(+) and OH center dot are the major active species, and a possible mechanism degradation pathway of MO dye is proposed.

Abstract The main etiological agents in dermatophytosis of human skin and nails are Trichophyton, in particular Trichophyton rubrum (T. rubrum) and Trichophyton mentagrophytes (T. mentagrophytes). A new series of twenty-three 3- and 4-arylcoumarins was synthesized and the antifungal activities against clinical isolates of T. rubrum and T. mentagrophytes were evaluated. Sixteen out of twenty-three molecules exhibited antifungal activity against one or both fungi strains. In some cases, the activity against T. rubrum has been comparable to fluconazole, one of the standards, being 8-methoxy-3-(4'-nitrophenyl)coumarin (16) the best compound within this series (minimum inhibitory concentration, MIC=6.25 mu g/mL). The preliminary structure-activity relationship study showed that the antifungal activity depends on the position and nature of the substitution patterns. The cytotoxicity of eleven compounds on D-384 (astrocytoma), A-549 (lung cancer) and RKO (colorectal cancer) cell lines was also performed. With the aim of deeply understand the potential of these molecules as hits to develop new drugs, the theoretical absorption, distribution, metabolism and excretion (ADME) properties of the active compounds were calculated.

Abstract Central nervous system (CNS) diseases, such neurodegenerative disorders (NDs) are increasing over the last years as a consequence of a continuous growing of the life expectancy and aging of population. The molecular mechanisms underlying the pathophysiology of NDs are still not fully understood. Neurodegeneration seems to be multifactorial and associated to a complex set of events comprising oxidative stress, inflammation, protein dysfunction and aggregation, among others, that at the end lead to the demise of neurons. It has been advocated that oxidative stress induced by imbalanced redox states, involving either overproduction of reactive species or dysfunction of the antioxidant system, and the higher levels of iron in the brain has a crucial role in NDs progression. Therefore, antioxidant therapy emerged as a useful approach to modulate oxidative stress events. However, despite the promising results obtained in in vitro cell-free and cell-based assays, the pharmacokinetics/pharmacodynamics properties of the majority of antioxidants preclude their advance in pre- and clinical trials. In this chapter the nonenzymatic endogenous and exogenous antioxidants (single and combined antioxidant therapy) currently in clinical trials, as drugs or supplements, for treatment of NDs will be highlighted. From the data one can conclude that the clinical trials performed so far related with single or combined antioxidants are still in a very early stage. So, a huge research space in the antioxidant field remains to be explored that hopefully will yield new and effective neuroprotective agents in a foreseeable future.

Abstract Oxidative stress is characterized by an imbalanced redox state that is principally related with a plethora of radical reactions skilled to trigger several pathophysiological mechanisms. So, the antioxidant therapy based on uptake of exogenous dietary antioxidants emerged as a useful approach to modulate the progression of oxidative stress-related events. Among dietary antioxidants, promising results have been obtained in in vitro cell-free and cell-based assays for huperzine A, α-lipoic acid, vitamins C and E, resveratrol, curcumin, epigallocatechin-3-gallate, and phenolic acids. However, the lack of drug-like pharmacokinetic properties precludes their advance in pre-and clinical trials. Although some dietary antioxidants, such as huperzine A, α-lipoic acid, resveratrol, and quercetin, were described to be able to surpass the blood-brain barrier, they have not been approved yet. Thus, new strategies have emerged by means of central chemical modifications or the use of nanoplatforms, along with new administration routes, which can facilitate their delivery across the blood-brain barrier.

Abstract Although Solanum nigrum L. is a phytoremediator for different metals, its growth and physiology are still compromised by toxic levels of zinc (Zn). Thus, the development of eco-friendly strategies to enhance its tolerance, maintaining remediation potential is of special interest. This study evaluated the potential of 24-epibrassinolide (24-EBL) to boost S. nigrum defence against Zn towards a better growth rate and remediation potential. After 24 days of exposure, the results revealed that Zn-mediated inhibitory effects on biomass and biometry were efficiently mitigated upon application of 24-EBL, without affecting Zn accumulation. The evaluation of oxidative stress markers reported that Zn excess stimulated the accumulation of superoxide anion (O-2(center dot-)), but reduced hydrogen peroxide (H2O2) levels, while not altering lipid peroxidation (LP). This was accompanied by an up-regulation of the antioxidant system, especially proline, superoxide dismutase (SOD) and ascorbate peroxidase (APX) in both organs, and ascorbate in roots of Zn-exposed plants. Foliar application of 24-EBL, however, induced distinctive effects, lowering proline levels in both organs, as well as APX activity in shoots and SOD in roots, whilst stimulating GSH and total thiols in both organs, as well as SOD and APX activity, in shoots and in roots, respectively. Probably due to a better antioxidant efficiency, levels of O-2(center dot-) and H2O2 in pre-treated plants remained identical to the control, while LP further decreased in shoots. Overall, our results indicate a protective effect of 24-EBL on S. nigrum response to excess Zn, contributing for a better tolerance and growth rate, without disturbing its phytoremediation potential.

Abstract In this Letter, we report the first observation of the capacitance-potential hysteresis at the ionic liquid vertical bar electrode interface in atomistic molecular dynamics simulations. While modeling the differential capacitance dependence on the potential scan direction, we detected two long-living types of interfacial structure for the BMImPF(6) ionic liquid at specific charge densities of the gold Au(111) surface. These structures differ in how counterions overscreen the surface charge. The high barrier for the transition from one structure to another slows down the interfacial restructuring process and leads to the marked capacitance-potential hysteresis.

Abstract <jats:p>Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...]</jats:p>