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Heavy metal tolerant plants have phytoremediation potential for the recovery of contaminated soils, and the characterization of their metabolic adaptation processes is an important starting point to elucidate their tolerance mechanisms at molecular, biochemical and physiological levels. In this research, the effects of Cd and Pb on growth and protein carbonylation in tissues of Paspalum fasciculatum exposed to 30 and 50 mg·Kg−1 Cd and Pb respectively were determined. P. fasciculatum seedlings exposed to metals grew more than controls until 60 days of cultivation and limited their oxidative effects to a reduced protein group. Carbonyl indexes in leaf and root proteins reached a significant increase concerning their controls in plants exposed 30 days to Cd and 60 days to Pb. From the combined approach of Western Blot with Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and protein analysis by Matrix Asisted Laser Desorption/Ionisation-Time Of Flight (MALDI-TOF/TOF) mass spectrometry, chloroplastic proteins were identified into the main oxidative stress-inducible proteins to Cd and Pb, such as subunits α, γ of ATP synthetase, Chlorophyll CP26 binding protein, fructose-bisphosphate aldolase and long-chain ribulose bisphosphate carboxylase (RuBisCO LSU). Cd generated damage in the photosynthetic machinery of the leaves of P. fasciculatum into the first 30 days of treatment; five of the oxidized proteins are involved in photosynthesis processes. Moreover, there was a proteolytic fragmentation of the RuBisCO LSU. Results showed that intrinsic tolerance of P. fasciculatum to these metals reached 60 days in our conditions, along with the bioaccumulating appreciable quantities of metals in their roots.

Background: Neurodegenerative disorders such as Alzheimer's disease show an alarming prevalence in the population, with around 50 million affected individuals worldwide, and is associated with the development of dementia, mainly affecting the elderly population. Currently, the treatments used are based on slowing the progression of the clinical symptoms of Alzheimer’s; however, no specific treatment has been found that induces reversion of the disease. Natural products may induce a wide range of palliative effects, such as ginseng (Panax ginseng), which produces secondary metabolites called ginsenosides, which have multiple therapeutic applications, including for neurodegenerative diseases such as Alzheimer’s. Methods: A virtual screening was carried out, using the CHEMBL database to find analogs of ginsenosides based on the ginsenoside Rg1 (CHEMBL501637). Next, the molecules were optimized and their format modified. The structure of BACE1 was downloaded from the Protein Data Bank database (ID: 1FKN) and prepared for the development of molecular docking using the PyRx software. A database of the ligands was created and molecular docking experiments were carried out, obtaining affinity energy values ​​in Kcal/mol. Results: Of the 27 analogues studied, it was found that the molecules CHEMBL451292, CHEMBL510371 and CHEMBL503302 showed considerable affinity with BACE1 when compared with the reference molecules (verubecestat and donepezil). These affinity energy values for CHEMBL451292, CHEMBL510371 and CHEMBL503302 ​​were -9.6, -8.1 and -7.6 Kcal/mol, respectively. Likewise, the binding site of the ligands to BACE1 were identified, with the main interactions being van der Waals and hydrogen bonding. Conclusions: Three ginsenoside analogues showed a similar binding energy with BACE1 compared to the reference drugs. The residues involved in the inhibitory activity of BACE1 and the type of predominant interactions were identified, which agreed with previous reports.

Background: Lipocalins play a role in the cellular trafficking of pheromones and are involved in allergic responses to domestic pets. However, the cross-reactivity among allergens of this group has been poorly explored, and the pheromone linking capacity is not well characterized. The aim of this study was to explore cross-reactive epitopes and pheromone linking capacity among Rat n 1 and homologues in domestic pets through an in silico approach. Methods: ElliPro and BepiPred in silico tools were used to predict B cell linear and cross-reactive epitopes. The pheromone linking capacity was explored by docking virtual screening with 2-ethylhexanol, 2,5-dimethylpyrazine, 2-sec-butyl-4,5-dihydrothiazole, and 2-heptanone ligands. Results: According to the analysis, Rat n 1 shares 52% identity with Equ c 1, Can f 6, Fel d 4, and Mus m 1 allergens. The overlapping structures assay revealed high structural homology (root mean square deviation < 1). Four lineal and three discontinuous epitopes were predicted on Ra t n 1. A lineal epitope located between amino acids residues 24 and 36 was highly conserved on all allergens explored. A cross-reactive discontinuous epitope (T142, K143, D144, L145, S146, S147, D148, K152, L170, T171, T173, D174) was also found. Docking molecular simulations revealed the active site, and we identified the properties of the binding of four pheromones and the binding potential of Rat n 1. Critical residues for interactions are reported in this study. Conclusions: We identified some possible allergens from Rattus norvegicus, and those allergens could have cross-reactivity with allergens from some animals. The results need to be confirmed with in vitro studies and could be utilized to contribute to immunotherapy and reduce allergic diseases related to lipocalins.

Introduction: The 5-HT1B receptor has a potential role in various psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. The objective of this study was to perform docking and molecular dynamics simulation to evaluate at atomic level the behavior of N,N-dimethyltryptamine (DMT) on 5-HT1B receptor.Methods: In this study, initially, a search for DMT was performed using the PubChem database. Subsequently, molecular docking was executed using AutoDock Vina based in PyRx 0.8 with a 95% analogy. Additionally, ergotamine (ERG) and serotonin were used as control. Then, it ran a total of 100 ns molecular dynamics simulations on 5-HT1B bound with DMT, serotonin, 112814775, and ERG. Finally, pharmacokinetic prediction and IV acute toxicity for analogues and DMT were performed.Results: It was possible to show that 112814775 had the lowest binding energy with the receptor. In addition, 112814775 presented great conformational stability, low mobility, and stiffness compared to the control ligands: ERG, serotonin, and DMT subsequent dynamic analysis. With respect to the free energy calculation, contributions such as Van der Waals, electrostatics, and nonpolar interactions for all systems, were highlighted.Conclusion: 112814775 showed affinities with 5-HT1B receptor and evidenced notable behavior by molecular dynamic simulation according to root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), the radius of gyration, number of hydrogen bond, and free energy calculated. These results established the possible relevance of in-silico studies in search of DMT analogues against the 5-HT1B receptor, which may be associated with alterations such as depression and anxiety, and may become future study molecules for the treatment of this type of disorder.