We compared the prevalence of levofloxacin (LVX) resistance with that of ofloxacin (OFX) and moxifloxacin (MFX) among multidrug resistant (MDR)MTBclinical isolates collected in Medellin, Colombia, between 2004 and 2009 and aimed at unraveling the underlying molecular mechanisms that explain the correlation between QRDR-A mutations and LVX resistance phenotype. We tested 104 MDR isolates for their susceptibility to OFX, MFX, and LVX. Resistance to OFX was encountered in 10 (9.6%) of the isolates among which 8 (7.7%) were also resistant to LVX and 6 (5.7%) to MFX. Four isolates resistant to the 3 FQ were harboring the Asp94Gly substitution, whilst 2 other isolates resistant to OFX and LVX presented the Ala90Val mutation. No mutations were found in the QRDR-B region. The molecular modeling of the interaction between LVX and the DNA-DNA gyrase complex indicates that the loss of an acetyl group in the Asp94Gly mutation removes the acid base interaction with LVX necessary for the quinolone activity. The Ala90Val mutation that substitutes a methyl for an isopropyl group induces a steric modification that blocks the LVX access to the gyrase catalytic site.

Diabetic retinopathy (RD) is a microvascular disease that can cause the formation of fragile neovessels, increasing the risk of hemorrhages and leading to vision loss. Current therapies are based on the intravitreal injection of anti-VEGF (vascular endothelial growth factor), which is invasive and can cause secondary effects. The development of new treatments that complement the current therapies is necessary to improve the patient’s outcomes. Nanostructured formulations offer several advantages regarding drug delivery and penetration. In this research, a resveratrol nanosuspension (RSV-NS) was prepared and characterized using dynamic light scattering, field emission scanning electron microscopy, and infrared spectroscopy. The RSV-NS had an average particle size of 304.0 ± 81.21 nm with a PDI of 0.225 ± 0.036, and a spherical-like morphology and uniform particle distribution. Cell viability, proliferation, and migration were tested on endothelial cells (HMRECs). RSV-NS in a concentration of less than 18.75 µM did not have a cytotoxic effect on HMRECs. Likewise, proliferation and migration were significantly reduced compared to the unstimulated control at 37.5 µM. The RSV-NS did not present cytotoxic effects but decreased cell proliferation and migration, indicating that it could provide an important contribution to future medical implementations and could have a high potential to treat this disease.

The occurrence of bone-related disorders and diseases has dramatically increased in recent years around the world. Demineralized bone matrix (DBM) has been widely used as a bone implant due to its osteoinduction and bioactivity. However, the use of DBM is limited because it is a particulate material, which makes it difficult to manipulate and implant with precision. In addition, these particles are susceptible to migration to other sites. To address this situation, DBM is commonly incorporated into a variety of carriers. An injectable scaffold has advantages over bone grafts or preformed scaffolds, such as the ability to flow and fill a bone defect. The aim of this research was to develop a DBM carrier with such viscoelastic properties in order to obtain an injectable bone substitute (IBS). The developed DBM carrier consisted of a PVA/glycerol network cross-linked with borax and reinforced with CaCO₃ as a pH neutralizer, porosity generator, and source of Ca. The physicochemical properties were determined by an injectability test, FTIR, SEM, and TGA. Porosity, degradation, bioactivity, possible cytotoxic effect, and proliferation in osteoblasts were also determined. The results showed that the developed material has great potential to be used in bone tissue regeneration.

Alzheimer’s disease pathology is characterized by β-amyloid plaques and neurofibrillary tangles. Amyloid precursor protein is processed by β and γ secretase, resulting in the production of β-amyloid peptides with a length ranging from 38 to 43 amino acids. Presenilin 1 (PS1) is the catalytic unit of γ-secretase, and more than 200 PS1 pathogenic mutations have been identified as causative for Alzheimer’s disease. A complete monocrystal structure of PS1 has not been determined so far due to the presence of two flexible domains. We have developed a complete structural model of PS1 using a computational approach with structure prediction software. Missing fragments Met1-Glut72 and Ser290-Glu375 were modeled and validated by their energetic and stereochemical characteristics. Then, with the complete structure of PS1, we defined that these fragments do not have a direct effect in the structure of the pore. Next, we used our hypothetical model for the analysis of the functional effects of PS1 mutations Ala246GLu, Leu248Pro, Leu248Arg, Leu250Val, Tyr256Ser, Ala260Val, and Val261Phe, localized in the catalytic pore. For this, we used a quantum mechanics/molecular mechanics (QM/MM) hybrid method, evaluating modifications in the topology, potential surface density, and electrostatic potential map of mutated PS1 proteins. We found that each mutation exerts changes resulting in structural modifications of the active site and in the shape of the pore. We suggest this as a valid approach for functional studies of PS1 in view of the possible impact in substrate processing and for the design of targeted therapeutic strategies.

Este estudio se centró en la formulación y caracterización de nanopartículas de plata (AgNP) funcionalizadas con d-limoneno. Las nanopartículas se funcionalizaron por inversión de fase y la síntesis de las nanopartículas se realizó in situ; se determinó el tamaño de partícula por difracción laser, potencial zeta y estabilidad coloidal óptica utilizando Multiscan 20 por un periodo de 24 horas a 37 °C; se determinó la concentración mínima inhibitorio (CMI) y la concentración mínima bactericida (CMB) del material formulado sobre las bacterias Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, Klebsiella oxytoca ATCC 700324, Enterococcus casseliflavus ATCC 700327, Escherichia coli BLEE+, Pseudomona aeruginosa resistente a carbapenémicos. Las nanopartículas presentaron estabilidad coloidal a una concentración de d-limoneno del 3,93 %, iones plata al 1,61x0-3 %, coadyuvante no iónico al 24 % y ácido ascórbico al 5,88 %; cómo sistema regulador se utilizó ácido cítrico/citrato (1:1) 0,48M para un pH de 4,5. La formulación se clasificó como un sistema polidisperso (PD = 0,0851), con una potencial zeta de -11,6 mV y tamaño promedio de partícula de 81,5 ± 0,9 nm. Se evidenció una velocidad de migración de partícula de -0,199 ± 0,006 mm h-1, un perfil de transmisión constante y perfil de retrodispersión con variaciones del 10 %, lo que representa una formulación estable. Las nanopartículas presentaron una CMI y una CMB de 28 μg mL-1 (5,6x10-2 % d-limoneno y 4,7x10-5 % AgNP) contra todas las bacterias probadas.

A set of methylimidazolium-furanchalcone hybrids and 1-alkyl-3-methylimidazolium salts were tested in order to find their antimicrobial activity against five gram positive bacteria, two gram negative bacteria and three fungi. In the series of 1-alkyl-3-methylimidazolium salts, compounds 4 and 7 were the most active compounds against S. mutans and F. oxysporum, respectively (MIC value of 3.0 and 6.7 mM, respectively). In addition, among the hybrid molecules, compound 10 exhibited the highest activity against F. solani (MIC₅₀ = 14.3 mM) followed by hybrid 11 (MIC₅₀ = 14.5 mM), which was also the most active against S. aureus, S. mutans (MIC₅₀ = 14.6, 18.7 mM, respectively). The activity of these hybrids was even better with regard to the lead compounds (furanchalcone, methylimidazole or the mixture). In the structure-activity relationship there was observed higher bioactivity when the alkyl linker had eigth carbon atoms. This was then supported by the in silico study which displayed a strong relationship between the length of the alkyl chain on N and the biological activity. The results highlight the importance of these derivatives (1-alkyl-3-methylimidazolium salts) and hybrids (methylimidazolium-furanchalcone) as potential antimicrobial agents.