Susceptibility of Candida biofilms to photodynamic treatment

Dissertação de mestrado em Bioengenharia

Synthesis and characterization of novel 4H-pyran-4-ylidene indole-based heterocyclic systems for several optical applications

The development of organic materials displaying high two-photon absorption (TPA) has attracted much attention in recent years due to a variety of potential applications in photonics and optoelectronics, such as three-dimensional optical data storage, fluorescence imaging, two-photon microscopy, optical limiting, microfabrication, photodynamic therapy, upconverted lasing, etc. The most frequently employed structural motifs for TPA materials are donor–pi bridge–acceptor (D–pi–A) dipoles, donor–pi bridge–donor (D–pi–D) and acceptor–pi bridge-acceptor (A–pi–A) quadrupoles, octupoles, etc. In this work we present the synthesis and photophysical characterization of quadrupolar heterocyclic systems with potential applications in materials and biological sciences as TPA chromophores. Indole is a versatile building block for the synthesis of heterocyclic systems for several optoelectronic applications (chemosensors, nonlinear optical, OLEDs) due to its photophysical properties and donor electron ability and 4H-pyran-4-ylidene fragment is frequently used for the synthesis of red light-emitting materials. On the other hand, 2-(2,6-dimethyl-4H-pyran-4-ylidene)malononitrile (1) and 1,3-diethyl-dihydro-5-(2,6-dimethyl-4H-pyran-4-ylidene)-2-thiobarbituric (2) units are usually used as strong acceptor moieties for the preparation of π-conjugated systems of the push-pull type. These building blocks were prepared by Knoevenagel condensation of the corresponding ketone precursor with malononitrile or 1,3-diethyl-dihydro-2-thiobarbituric acid. The new quadrupolar 4H-pyran-4-ylidene fluorophores (3) derived from indole were prepared through condensation of 5-methyl-1H-indole-3-carbaldehyde with the acceptor precursors 1 and 2, in the presence of a catalytical amount of piperidine. The new compounds were characterized by the usual spectroscopic techniques (UV-vis., FT-IR and multinuclear NMR - 1H, 13C).

Phage therapy: a step forward in the treatment of Pseudomonas aeruginosa infections

Antimicrobial resistance constitutes one of the major worldwide public health concerns. Bacteria are becoming resistant to the vast majority of antibiotics and nowadays, a common infection can be fatal. To revert this situation, the use of phages for the treatment of bacterial infections has been extensively studied as an alternative therapeutic strategy. Since P. aeruginosa is one of the most common causes of healthcare-associated infections, many studies have reported the in vitro and in vivo antibacterial efficacy of phage therapy against this bacterium. This review collects data of all the P. aeruginosa phages sequenced to date, providing a better understanding about their biodiversity. This review will further address the in vitro and in vivo results obtained by using phages to treat or prevent P. aeruginosa infections as well as the major hurdles associated with this therapy.

Development of folate-targeted liposomes for rheumatoid arthritis therapy

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for Monocarboxylate Transporters as metabolic targets for therapy.

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.

The diagnostic and prognostic role of liquid-based cytology: are we ready to monitor therapy and resistance?

Here, we evaluate the diagnostic and prognostic role of liquid-based cytology (LBC) in different body lesions, including thyroid, lung, effusions and malignant breast lesions. LBC has gained consensus after being applied to both non-gynecologic and fine-needle aspiration cytology. Although some remain sceptical regarding the diagnostic efficacy of LBC, mainly when used alone, in recent years, good results have been obtained as long as it showed a high diagnostic accuracy. Here, we discuss the additional possibility of storing material for the application of ancillary techniques (immunocytochemistry–molecular analysis) with several diagnostic and prognostic advantages, which may pave the way for the challenging evaluation of both monitoring responses to treatment and resistance to targeted therapies in thyroid, lung, breast carcinoma or malignant effusions. Furthermore, it provides the use of several molecular spots as specific targets for personalized therapy.

Glucose addiction in cancer therapy : advances and drawbacks

Glucose addiction in cancer therapy: advances and drawbacks.