Triple negative breast cancer: nanosolutions for a big challenge

Triple negative breast cancer (TNBC) is a particular immunopathological subtype of breast cancer that lacks expression of estrogen and progesterone receptors (ER/PR) and amplification of the human epidermal growth factor receptor 2 (HER2) gene. Characterized by aggressive and metastatic phenotypes and high rates of relapse, TNBC is the only breast cancer subgroup still lacking effective therapeutic options, thus presenting the worst prognosis. The development of targeted therapies, as well as early diagnosis methods, is vital to ensure an adequate and timely therapeutic intervention in patients with TNBC. This review intends to discuss potentially emerging approaches for the diagnosis and treatment of TNBC patients, with a special focus on nano-based solutions that actively target these particular tumors.

Candida bracarensis: Evaluation of virulence factors and its tolerance to Amphotericin B and Fluconazole

Candida bracarensis is an uncommon Candida species found during an epidemiological study of candidiasis performed in Braga, Portugal. Initially, it was identified as C. glabrata, but recently detailed analyses pointed out their differences. So, little information is still available about C. bracarensis virulence factors and antifungal susceptibilities. Therefore, the main goal of this work is to evaluate the ability of C. bracarensis to form biofilms, to produce hydrolytic enzymes (proteases, phospholipases and hemolysins), as well as its susceptibility to amphotericin B and fluconazole. It was shown, for the first time, that all C. bracarensis strains were able to form biofilms and display proteinase and hemolytic activities. Moreover, although planktonic cells presented antifungal susceptibility, amphotericin B and fluconazole were unable to inhibit biofilm formation and eradicate pre-formed biofilms. Due to the propensity of C. bracarensis to display antifungal resistance and virulence attributes, the control of these emerging pathogens is recommended.

Antibacterial activity of textiles for wound treatment

Major advances in the development and use of antimicrobial textiles to control bacterial proliferation on wound beds continue. However, wound dressings are, in general, not included in standardized regimens for measuring and monitoring their antimicrobial effectiveness. This work adapts these methods to assess the antibacterial activity of textiles designed for wound healing purposes. Environmental conditions representative of those present at the wound site (i.e., moisture levels, infection, and available nutrients) were evaluated. This work shows that moisture levels were the environmental factor that had the greatest influence on the antimicrobial agent activities tested. These results suggest that it is possible to use the more representative environmental conditions present on the wound bed for in vitro screening of textile antimicrobial activity.

Evaluation of antibacterial activity of caffeic acid encapsulated by -cyclodextrins

Context: Caffeic acid is described as antibacterial, but this bioactive molecule has some issues regarding solubility and stability to environmental stress. Thus, encapsulation devices are required. Objective: The aim of this work was to study the effect of the caffeic acid encapsulation by cyclodextrins on its antibacterial activity. Materials and methods: The interactions between the caffeic acid and three cyclodextrins (-cyclodextrin (CD), 2-hydroxypropyl--cyclodextrin (HPCD) and methyl--cyclodextrin were study. Results and discussion: The formation of an aqueous soluble inclusion complex was confirmed for CD and HPCD with a 1:1 stoichiometry. The CD/caffeic acid complex showed higher stability than HPCD/caffeic acid. Caffeic acid antibacterial activity was similar at pH 3 and pH 5 against the three bacteria (K. pneumoniae, S. epidermidis and S. aureus). Conclusions: The antibacterial activity of the inclusion complexes was described here for the first time and it was shown that the caffeic acid activity was remarkably enhanced by the cyclodextrins encapsulation.

Algorithms and tools for in silico design of cell factories

PhD thesis in Bioengineering

Modeling microbes: New methods for integrated metabolic and regulatory network reconstruction

PhD Thesis in Bioengineering

Improvement of in silico strain engineering methods in Saccharomyces cerevisiae

PhD thesis in Bioengineering

[Editorial] Current challenges in modeling cellular metabolism

The authors would like to thank the financial support from the NovoNordiskFoundation.

Hair coloration by gene regulation: fact or fiction?

The unravelling of hair pigmentation genetics and robust delivery systems to the hair follicle (HF) will allow the development of a new class of colouring products. The challenge will be changing hair colour from inside out by safely regulating the activity of target genes through the specific delivery of synthetic/natural compounds, proteins, genes, or small RNAs.

Relationship between galactomannan structure and physicochemical properties of films produced thereof

In this work five sources of galactomannans, Adenanthera pavonina, Cyamopsis tetragonolobus, Caesalpinia pulcherrima, Ceratonia siliqua and Sophora japonica, presenting mannose/galactose ratios of 1.3, 1.7, 2.9, 3.4 and 5.6, respectively, were used to produce galactomannan-based films. These films were characterized in terms of: water vapour, oxygen and carbon dioxide permeabilities (WVP, O 2 P and CO 2 P); moisture content, water solubility, contact angle, elongation-at-break (EB), tensile strength (TS) and glass transition temperature (T g ). Results showed that films properties vary according to the galactomannan source (different galactose distribution) and their mannose/galactose ratio. Water affinity of mannan and galactose chains and the intermolecular interactions of mannose backbone should also be considered being factors that affect films properties. This work has shown that knowing mannose/galactose ratio of galactomannans is possible to foresee galactomannan-based edible films properties.

In silico constraint-based strain optimization methods: the quest for optimal cell factories

Shifting from chemical to biotechnological processes is one of the cornerstones of 21st century industry. The production of a great range of chemicals via biotechnological means is a key challenge on the way toward a bio-based economy. However, this shift is occurring at a pace slower than initially expected. The development of efficient cell factories that allow for competitive production yields is of paramount importance for this leap to happen. Constraint-based models of metabolism, together with in silico strain design algorithms, promise to reveal insights into the best genetic design strategies, a step further toward achieving that goal. In this work, a thorough analysis of the main in silico constraint-based strain design strategies and algorithms is presented, their application in real-world case studies is analyzed, and a path for the future is discussed.

Influence of glucose concentration on the structure and quantity of biofilms formed by Candida parapsilosis

Candida parapsilosis is nowadays an emerging opportunistic pathogen and its increasing incidence is part related to the capacity to produce biofilm. In addition, one of the most important C. parapsilosis pathogenic risk factors includes the organisms\textquoteright selective growth capabilities in hyper alimentation solutions. Thus, in this study, we investigated the role of glucose in C. parapsilosis biofilm modulation, by studying biofilm formation, matrix composition and structure. Moreover, the expression of biofilm-related genes (BCR1, FKS1 and OLE1) were analyzed in the presence of different glucose percentages. The results demonstrated the importance of glucose in the modulation of C. parapsilosis biofilm. The concentration of glucose had direct implications on the C. parapsilosis transition of yeast cells to pseudohyphae. Additionally, it was demonstrated that biofilm related genes BCR1, FKS1 and OLE1 are involved in biofilm modulation by glucose. The mechanism by which glucose enhances biofilm formation is not fully understood, however with this study we were able to demonstrate that C. parapsilosis respond to stress conditions caused by elevated levels of glucose by up-regulating genes related to biofilm formation (BCR1, FKS1 and OLE1).

(Un)suitability of the use of pH buffers in biological, biochemical and environmental studies and their interaction with metal ions - a review

The use of buffers to maintain the pH within a desired range is a very common practice in chemical, biochemical and biological studies. Among them, zwitterionic N-substituted aminosulfonic acids, usually known as Good's buffers, although widely used, can complex metals and interact with biological systems. The present work reviews, discusses and updates the metal complexation characteristics of thirty one commercially available buffers. In addition, their impact on biological systems is also presented. The influences of these buffers on the results obtained in biological, biochemical and environmental studies, with special focus on their interaction with metal ions, are highlighted and critically reviewed. Using chemical speciation simulations, based on the current knowledge of the metal-buffer stability constants, a proposal of the most adequate buffer to employ for a given metal ion is presented.

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.

Extracting kinetic information from literature with KineticRE

To better understand the dynamic behavior of metabolic networks in a wide variety of conditions, the field of Systems Biology has increased its interest in the use of kinetic models. The different databases, available these days, do not contain enough data regarding this topic. Given that a significant part of the relevant information for the development of such models is still wide spread in the literature, it becomes essential to develop specific and powerful text mining tools to collect these data. In this context, this work has as main objective the development of a text mining tool to extract, from scientific literature, kinetic parameters, their respective values and their relations with enzymes and metabolites. The approach proposed integrates the development of a novel plug-in over the text mining framework @Note2. In the end, the pipeline developed was validated with a case study on Kluyveromyces lactis, spanning the analysis and results of 20 full text documents.