Applying loop-mediated isothermal amplification (LAMP) in the diagnosis of malaria, leishmaniasis and trypanosomiasis as point-of-care tests (POCTs)

One of the main objectives of the WHO is controlling transmission of parasitic protozoa vector- borne diseases. A quick and precise diagnosis is critical in selecting the optimal therapeutic regime that avoids unnecessary treatments and the emergence of resistance. Molecular assays based on Loop- Mediated Isothermal Amplification (LAMP) techniques are a good alternative to light microscopy and antigen-based rapid diagnostic tests in developing countries, since they allow for a large amount of genetic material generated from a few copies of DNA, and use primers that lead to high sensitivity and specificity, while the amplification process can be performed in isothermal conditions without the need of sophisticated equipment to interpret the results. In this review, the main advances in the development of LAMP assays for the diagnosis of malaria, leishmaniasis and Chagas' disease are discussed as well as the feasibility of their implementation in developing countries and use as point- of-care diagnostic tests

Alkaloids as Photosensitisers for the Inactivation of Bacteria

Antimicrobial photodynamic therapy has emerged as a powerful approach to tackle microbial infections. Photodynamic therapy utilises a photosensitiser, light, and oxygen to generate singlet oxygen and/or reactive oxygen species in an irradiated tissue spot, which subsequently react with nearby biomolecules and destroy the cellular environment. Due to the possibility to irradiate in a very precise location, it can be used to eradicate bacteria, fungus, and parasites upon light activation of the photosensitiser. In this regard, natural products are low-cost molecules capable of being obtained in large quantities, and some of them can be used as photosensitisers. Alkaloids are the largest family among natural products and include molecules with a basic nature and aromatic rings. For this study, we collected the naturally occurring alkaloids used to treat microorganism infections using a photodynamic inactivation approach. We gathered their main photophysical properties (excitation/emission wavelengths, quantum yields, and oxygen quantum yield) which characterise the ability to efficiently photosensitise. In addition, we described the antibacterial activity of alkaloids upon irradiation and the mechanisms involved in the microorganism killing. This review will serve as a reference source to obtain the main information on alkaloids used in antimicrobial photodynamic therapy

The lipid network of plasma extracellular vesicles reveals sex-based differences in the lipidomic profile of alcohol use disorder patients

Code and data used for the bioinformatics approach. language R Contains the code used to carry out this project. It presents the different sections: 00Data 01Functions 02Preprocessing_&_ExploratoryAnalysis 03DifferentialAbundanceAnalysis 04ClassAnnotation 05LSEA 06LINE

N-(2-methyl-indol-1H-5-yl)-1-naphthalenesulfonamide: a novel reversible antimitotic agent inhibiting cancer cell motility

A series of compounds containing the sulfonamide scaffold were synthesized andscreened for their in vitro anticancer activity against a representative panel of human cancer cell lines, leading to the identification ofN-(2-methyl-1H-indol-5-yl)-1-naphthalenesulfonamide (8e) as a compound showing a remarkable activity across the panel, with IC50 values in the nanomolar-to-low micromolar range. Cell cycle distribution analysis revealed that 8e promoted a severe G2/M arrest, which was followed by cellular senescence as indicated by the detection of senescence-associated -galactosidase (SA-gal) in 8e-treated cells. Prolonged 8e treatment also led to the onset of apoptosis, in correlation with the detection of increased Caspase 3/7 activities. Despite increasing-H2A.X levels, a well-established readout for DNA double-strand breaks, in vitro DNA binding studies with 8e did not support interaction with DNA. In agreement with this, 8e failed to activate the cellular DNA damage checkpoint. Importantly, tubulin staining showed that 8e promoted a severe disorganization of microtubules and mitotic spindle formation was not detected in 8e-treated cells. Accordingly, 8e inhibited tubulin polymerization in vitro in a dose-dependent manner andwas also able to robustly inhibit cancer cell motility. Docking analysis revealed a compatible interaction with the colchicine-binding site of tubulin. Remarkably, thesecellular effects were reversible since disruption of treatment resulted in the reorganization of microtubules, cell cycle re-entry and loss of senescent markers. Collectively, our data suggest that this compound may be a promising new anticancer agent capable of both reducing cancer cell growth and motility

Identification of Aryl Polyamines Derivatives as Anti-<i>Trypanosoma cruzi</i> Agents Targeting Iron Superoxide Dismutase

Chagas disease (CD) is a tropical and potentially fatal infection caused by Trypanosoma cruzi. Although CD was limited to Latin America as a silent disease, CD has become widespread as a result of globalization. Currently, 6–8 million people are infected worldwide, and no effective treatment is available. Here, we identify new effective agents against T. cruzi. In short, 16 aryl polyamines were screened in vitro against different T. cruzi strains, and lead compounds were evaluated in vivo after oral administration in both the acute and chronic infections. The mode of action was also evaluated at the energetic level, and its high activity profile could be ascribed to a mitochondria-dependent bioenergetic collapse and redox stress by inhibition of the Fe-SOD enzyme. We present compound 15 as a potential compound that provides a step forward for the development of new agents to combat CD