Alzheimer's Disease (AD) is a neurodegenerative disease that causes the death of brain cells and is the leading cause of dementia. The disease is characterized by the progressive accumulation of plaques and neurofibrillary tangles formed by beta-amyloid peptides (Aβ), which lead to neuronal death and decline in cognition and memory. To mitigate this process, different mechanisms and molecular targets have been explored for the prospecting of new drugs, and computational techniques play an important role in this screening process. In this work, a combination of QSAR models was trained to facilitate the screening of molecules against different targets of AD. In addition, a multi-target screening of FDA-approved drugs was performed using the QSAR models and molecular docking, and an analysis of the hit molecules revealed the potential of this approach in the screening and repurposing of molecules for AD drug discovery.
Leishmaniosis has two main clinical forms: cutaneous and visceral leishmaniosis, which can leave serious sequelae and even cause death if not properly diagnosed and treated. Diagnostic methods include parasitological, immunological, or DNA amplification. Rapid immunochromatographic tests (ICTs) are considered the best option for an initial diagnosis of leishmaniosis at the point of care and disease control. This is because they are easy to use, interpret, and are low-cost. This paper reviews the diagnostic performance of commercial ICTs evaluated and published by various researchers. A total of 78 articles were found, 50 of which correspond to human leishmaniosis, and the other 28 address canine leishmaniosis. Many of these kits do not present high sensitivity and specificity, and their use as screening methods in endemic areas is problematic. Recombinant proteins rK39 and rK28 were used as antigens in the commercial test for diagnosing both human visceral leishmaniosis (VL) and canine visceral leishmaniosis (CVL), and they showed similar performance. However, a lot of discrepancies among authors related to sensitivity and specificity results make it difficult to choose or recommend any of these commercial ICTs for an effective diagnosis of leishmaniosis. Only the ICT with recombinant protein rKE16 showed good performance for VL diagnosis in Asia. In contrast, the CL Detect⢠Rapid Test, which uses peroxidoxin as an antigen, is the only approved test to diagnose cutaneous leishmaniosis (CL), but it showed low sensitivity on the three continents (Africa, Asia, and South America) where CL is endemic. The review conducted in this study indicates the need to consider the Leishmania species that are infecting the endemic area in the development of the antigen used in ICTs, together with the development of platforms and/or new techniques that increase the efficiency of ICTs.
Ulvan is the main sulfated polysaccharide isolated from green seaweeds of the genus Ulva, showing several biological properties. A fibrous ulvan-based mat exhibiting nanofibers with an average diameter of 144 ± 33 nm, was fabricated from electrospun of an aqueous mixture, composed by poly(vinyl alcohol) (PVA) and ulvan in a 5:2 mass ratio (PVA5U2). As expected from its composition, the PVA5U2 mat readily disintegrated upon contact with water, limiting potential uses. For this reason, mat stabilization against water exposition as well as keeping ulvan functional groups availability in the biomaterial, as fundamental aspects for functionalization purposes, became the main objectives of this work. To achieve them, thermal crosslinking (180 °C/60 min), instead of chemical crosslinking, was used for the first time in this type of biomaterial, modulating the poor stability of the ulvan-based electrospun mat in water and preventing the formation of polysaccharides crosslinking complexes during the stabilization treatment. Infrared spectroscopy and scanning electron microscopy were used to characterize the PVA5U2 mat and the thermally-crosslinked PVA5U2 mat, evidencing the presence of nanofibers and ulvan functional groups. Nanofibers increased 30% in diameter after 180 min of water exposition. The PVA5U2 mat exhibit characteristics that turn them into a versatile biotechnological biomaterial.
Fatty acids from macroalgae display various promising biological activities, including immunomodulatory activity. Here, we characterized the adjuvant potential of macroalgae lipid extracts in a recombinant vaccine against caseous lymphadenitis. Female BALB/c mice were divided into seven groups and immunized twice (Days 0 and 21) with 0.9% saline solution (G1); rCP01850 + saponin (G2); rCP01850 + Sarcopeltis skottsbergii gametophyte phase (SFG) (G3); rCP01850 + Sarcopeltis skottsbergii cystocarp phase (SFC) (G4); rCP01850 + Iridaea cordata cystocarp phase (IFC) (G5); rCP01850 + Iridaea cordata tetrasporophyte phase (IFT) (G6); or rCP01850 alone (G7). Blood samples were collected for total IgG, IgG1, and IgG2a quantification. Moreover, another assay measured the IFN-γ and IL-10 levels produced by each experimental group through in vitro stimulation of splenocytes with rCP01850. Groups G5 and G6 showed the highest antibody levels after day 42. Groups G3, G4, G5, and G6 significantly increased IgG1 levels when compared to G1 and G7, with no statistical difference between G3, G4, G5, and G6. Meanwhile, G5 and G6 showed a significantly higher increase in IgG2a levels than the other groups on day 42. Groups G3, G4, G5, and G6 significantly produced IL-10, while G3 and G5 showed the highest levels of IFN-γ (p < 0.05). We concluded that the lipid extracts of Sarcopeltis skottsbergii and Iridaea cordata, when associated with rCP01850, elicited both humoral and cellular immune responses and are, therefore, promising candidates as adjuvants in vaccines against caseous lymphadenitis.
