Neuropathic pain follows nervous system dysfunction or damage, significantly affecting patients’ quality of life. The need for more effective and safer pain management has drawn attention to voltage-gated sodium channels as druggable therapeutic targets in medicinal chemistry, leading to the discovery of various compounds with pharmacological potential, among which heterocycles with pyrazole and indolone cores have stood out for their versatility. Aiming to discover new potential modulators of neuropathic pain, this research studied a series of 35 compounds with a 3-hydroxy-3-pyrazolyl-1H-indolin-2-one nucleus (molecular hybrids with pyrazole and indolone cores) by bioavailability screening, using the computational tools MedChem DesignerTM and AdmetSar 2.0, which predicted good potential to cross biological barriers and suggested theoretically favorable safety profiles. The potential use of these compounds as modulators of the voltage-gated sodium channel NaV1.7 (PDB code: 6J8G), an important molecular target in the treatment of neuropathic pain, was evaluated using molecular docking with AutoDock suite and DOCK6 software. Docking protocols were validated by redocking crystallized endogenous ligands, and results were validated using the rank-consensus approach. From those computational studies, four compounds, with the highest rank consensus values (0.52-0.59), emerged as promising candidates for experimental assays as NaV1.7 modulators. This study highlights the importance of computer-aided rational design in the discovery of new compounds with therapeutic potential in the treatment of neuropathic pain.
The frequency of rare and orphan genetic diseases is high in some populations in the Colombian department of Boyacá. This is arguably associated with the elevated consanguinity in the region, which can increase autozygosity and the expression of recessive conditions. Surname sharing (Isonymy) analysis is useful for evaluating consanguinity, population migration patterns, and population structure. Here, we estimated inbreeding-related parameters via isonymy analysis to characterize the population structure of Boyacá and to assess whether population isolation is consistent with increased risk of rare genetic diseases in the region. Data were retrieved from national databases, such as the System of Potential Beneficiaries of Social Programs (SISBÉN) and the National Public Health Surveillance System (SIVIGILA). We also obtained information from a demographic and genealogical survey conducted with 1 033 participants in the department of Boyacá. Based on SISBÉN data, isonymy parameters were calculated to assess population isolation and relatedness, while reports of genetic diseases from SIVIGILA were analyzed to explore their relationship with kinship coefficients. This was complemented by genealogical surveys, principal coordinates analysis (PCoA), and cluster analysis. The highest kinship coefficients were found in the municipalities of Chíquiza and Pisba, and no correlation was found between the kinship coefficient and the municipality-level distribution of reported genetic disease cases. Overall, the isonymy parameters were comparable to those reported in population isolates, highlighting the presence of genetically isolated subpopulations in Boyacá. Such isolation is likely consistent with founder effects and local enrichment of rare variants. However, confirmation of a relationship with rare disease risk requires targeted genetic studies and improved epidemiological surveillance.
Amazonian fruits constitute a promising source of bioactive compounds with functional and nutraceutical potential, particularly their non-edible fractions such as peels and seeds, which are commonly discarded as agro-industrial residues. This study evaluated the bioactive compound content and antioxidant capacity of peels, seeds, and pulps of Pourouma cecropiifolia (uva caimarona), Myrciaria dubia (camu-camu), and Mauritia flexuosa (canangucha), as well as the effect of extraction solvents on metabolite recovery. Two 70 % (v/v) solvent mixtures, methanol/water and acetone/water, were evaluated. Extracted phenolic compounds, including flavonoids, anthocyanins, catechin, quercetin, gallic acid, and ascorbic acid, were quantified. Extract antioxidant capacities were assessed by radical-scavenging and reducing-power assays, and multivariate statistical analyses were applied to determine relationships between bioactive compounds and antioxidant capacity. Seeds of uva caimarona and camu-camu exhibited the highest concentrations of catechin, quercetin, and gallic acid. Canangucha peel stood out for its elevated content of phenolic compounds and ascorbic acid. Positive associations were observed between bioactive compounds and antioxidant capacity. Additionally, 70 % acetone was more efficient than 70 % methanol in extracting the evaluated metabolites. Overall, the non-edible fractions of the evaluated Amazonian fruits demonstrated high antioxidant potential, supporting their valorization as functional ingredients for food and nutraceutical applications.
In this study, biochar was obtained via pyrolysis from Dominico-Harton plantain (Musa AAB Simmonds) agricultural waste and surface-treated with FeSO4 to provide it with magnetic properties. This magnetic biochar was used to adsorb crystal violet and malachite green dyes dissolved in water. The morphology, porosity, and elemental composition of biochar were analyzed using scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM–EDX) before and after surface treatment. Additionally, biochar spectra were obtained before and after surface treatment, as well as after adsorption experiments, using Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy. The equilibrium kinetics of dye adsorption on magnetic biochar were evaluated using pseudo-first-order (PFO), pseudo-second-order (PSO), and intraparticle diffusion models. The results confirmed the presence of Fe in the biochar. Biochar’s maximum dye removal efficiencies were 99.06 % (𝑡 = 150 min) for crystal violet and 97.45 % (𝑡 = 180 min) for malachite green. The pseudo-second-order kinetic model best described the adsorption rate of dyes on the biochar surface, with 𝑅2 = 0.9933 (crystal violet) and 𝑅2 = 0.9979 (malachite green). This study also demonstrated that magnetic biochar can be successfully synthesized from Dominico-Harton plantain agricultural waste and used for the degradation of crystal violet and malachite green dyes in aqueous solutions.
Colombia is the second country with the highest number of Amerindian ethnic groups, with autonomy and self-governance, allowing them to preserve their culture and Amerindian genetic heritage. In some of these communities, studies using markers such as mitochondrial DNA (mtDNA), the non-recombining region of the Y chromosome (NRY), and Ancestry Informative Markers (AIMs) have helped clarify the settlement processes and genetic admixture of these populations. In this study, we analyzed genome-wide Single Nucleotide Polymorphism (SNP) data from four indigenous populations of Colombia, the Wayuu, Nasa-Páez, Pijao, and Embera-Kátio, genotyped on the Axiom SpainBA panel. We were interested in determining the genetic ancestry and structure, as well as patterns of genetic variation in these populations. We collected personal questionnaires to determine family relationships and included only unrelated individuals for further analyses. Population genetic analyses, including other Native and non-Indigenous American populations, showed genetic affinities to other Indigenous American populations and varied levels of genetic admixture with non-American sources. Furthermore, our analyses suggest that distinct demographic histories, including isolation, genetic drift associated with reduced effective population size (Ne), and admixture, have shaped patterns of genetic variation and population structure among Colombian Indigenous populations.
