Impact of Structural Observables From Simulations to Predict the Effect of Single-Point Mutations in MHC Class II Peptide Binders.

The prediction of peptide binders to Major Histocompatibility Complex (MHC) class II receptors is of great interest to study autoimmune diseases and for vaccine development. Most approaches predict the affinities using sequence-based models trained on experimental data and multiple alignments from known peptide substrates. However, detecting activity differences caused by single-point mutations is a challenging task.

Vitamin E TPGS 1000 Induces Apoptosis in the K562 Cell Line: Implications for Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a hematologic malignancy derived from the myeloid lineage molecularly characterized by t(9;22)(q34;q11) resulting in BCR-ABL1 gene fusion, which is known as Philadelphia (Ph) chromosome. Although tyrosine kinase inhibitors (TKIs) have restored and maintained the quality of life of patients with CML, an important minority of patients become resistant to first-and-second-generation TKIs and require an alternative treatment. The K562 cell (Ph+, p53-/-) line was treated with Vit E TPGS 1000 (20-80 M) only or with other products of interest (e.

A Bayesian approach to extracting free-energy profiles from cryo-electron microscopy experiments.

Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule's conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles.

New Hybrids Based on Curcumin and Resveratrol: Synthesis, Cytotoxicity and Antiproliferative Activity against Colorectal Cancer Cells.

We synthesized twelve hybrids based on curcumin and resveratrol, and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, along with the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids and (for SW480) and , and (for SW620) displayed the best cytotoxic activity with IC values ranging from 11.

Genetic and toxigenic diversity of group isolated from powdered foods.

is a human pathogenic bacterium that produces emetic and diarrheal foodborne diseases. This study evaluated the genetic and toxigenic diversity in group isolates from powdered foods collected in public educational institutions, bakeries and powdered food companies located in Medellín, Colombia. was detected in 35 of 305 (11%) powdered food samples and 52 were isolated.

Attentional bias during emotional processing: Behavioral and electrophysiological evidence from an Emotional Flanker Task.

Threatening stimuli seem to capture attention more swiftly than neutral stimuli. This attention bias has been observed under different experimental conditions and with different types of stimuli. It remains unclear whether this adaptive behaviour reflects the function of automatic or controlled attention mechanisms.

Effect of ibuprofen in vivo and in vitro on the sperm quality of the striped catfish Pseudoplatystoma magdaleniatum.

Because ibuprofen is a high consumption drug, which has the waters as its final destination, causing alterations in the aquatic environment, specifically in fish. However, there is not enough knowledge about the effect it can have on neotropical fish. This study aimed to evaluate the impact of different concentrations of ibuprofen on sperm quality, both in vivo and in vitro, of the striped catfish Pseudoplatystoma magdaleniatum, and analyze its effects on the reproduction of this critical extinction endangered species.

The Hydroalcoholic Extract of (Cat's Claw) Inhibits the Infection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) .

The coronavirus disease 2019 (COVID-19) has become a serious problem for public health since it was identified in the province of Wuhan (China) and spread around the world producing high mortality rates and economic losses. Nowadays, the WHO recognizes traditional, complementary, and alternative medicine for treating COVID-19 symptoms. Therefore, we investigated the antiviral potential of the hydroalcoholic extract of stem bark from Peru against SARS-CoV-2 .

Chemistry and Anticancer Activity of Hybrid Molecules and Derivatives based on 5-Fluorouracil.

Considering that cancer continues to be an important cause of death worldwide, several conventional anticancer treatments are widely used. However, most of them display low selectivity against malignant cells and induce many adverse side effects. Among these, the use of therapies based on 5-Fluorouracil (5-FU) has been one of the most efficient, with a broad-spectrum.

Monitoring of chlorine decay in public swimming pools in Medellín (Colombia).

The present work shows the evaluation of the decay of free residual chlorine in several public swimming pools in the city of Medellín, observing that a decrease in residual chlorine does occur. Some factors accelerate the decrease in the concentration of free residual chlorine in recreational water, such as the number of bathers in the pool, the pH, and the temperature of the water. For this reason, the concentration of the disinfectant rapidly decreases to an extent that the health of swimmers could be put at risk.

Multi-Target Effects of the Cannabinoid CP55940 on Familial Alzheimer's Disease PSEN1 E280A Cholinergic-Like Neurons: Role of CB1 Receptor.

Background: Alzheimer's disease (AD) is characterized by structural damage, death, and functional disruption of cholinergic neurons (ChNs) as a result of intracellular amyloid-β (Aβ) aggregation, extracellular neuritic plaques, and hyperphosphorylation of protein tau (p-Tau) overtime.

Objective: To evaluate the effect of the synthetic cannabinoid CP55940 (CP) on PSEN1 E280A cholinergic-like nerve cells (PSEN1 ChLNs)-a natural model of familial AD.

Methods: Wild type (WT) and PSEN1 ChLNs were exposed to CP (1μM) only or in the presence of the CB1 and CB2 receptors (CB1Rs, CB2Rs) inverse agonist SR141716 (1μM) and SR144528 (1μM) respectively, for 24 h.

Removal of As, As, Sb, and Hg ions from aqueous solutions by pure and co-precipitated akaganeite nanoparticles: adsorption kinetics studies.

Adsorption kinetics models have been used to evaluate the adsorption behaviour of pollutants on different materials but there are no reports for the adsorption of As, As, Sb and Hg on co-precipitated akaganeite nanoparticles which were previously formed in the presence of these ions. In this research, the performance of pure and co-precipitated akaganeite nanoparticles as adsorbents of As, As, Sb and Hg in aqueous solutions was evaluated using the nonlinear kinetics models of Langmuir, Lagergren, Ho-McKay, Bangham, Elovich and simplified Elovich. In addition, transmission Fe Mössbauer spectrometry was used for the first time to compare the physico-chemical properties of akaganeite before and after the adsorption processes.

Carvacrol: An Approach of a Candidate Drug on HER2, PI3K, mTOR, hER-, PR, and EGFR Receptors in the Breast Cancer.

Carvacrol is a phenol monoterpene found in aromatic plants specially in Lamiaceae family, which has been evaluated in an experimental model of breast cancer. However, any proposed mechanism based on its antitumor effect has not been reported. In our previous study, carvacrol showed a protective effect on 7,12-dimethylbenz[]anthracene- (DMBA-) induced breast cancer in female rats.

(cat's claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling.

COVID-19 is a novel severe acute respiratory syndrome coronavirus. Currently, there is no effective treatment and vaccines seem to be the solution in the future. Virtual screening of potential drugs against the S protein of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has provided small molecular compounds with a high binding affinity.

TPEN exerts selective anti-leukemic efficacy in ex vivo drug-resistant childhood acute leukemia.

Despite some advances in the treatment of acute lymphoblastic (ALL) and myeloid leukemia (AML) in recent years, there is still a prominent percentage of pediatric patients with a reduced overall prognosis. Therefore, other therapeutic approaches are needed to treat those patients. In the present study, we report that the metal chelator TPEN affected ΔΨ and DNA content in isolated CD34 refractory cells from bone marrow ALL (n = 7; B-cell, n = 4; T-cell, n = 3) and AML (n = 3) pediatric patients.

Investigating Potential Inhibitory Effect of (Cat's Claw) against the Main Protease 3CL of SARS-CoV-2 by Molecular Modeling.

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2. Presently, there is no effective treatment for COVID-19. As part of the worldwide efforts to find efficient therapies and preventions, it has been reported the crystalline structure of the SARS-CoV-2 main protease M (also called 3CL) bound to a synthetic inhibitor, which represents a major druggable target.

From discourse to pathology: Automatic identification of Parkinson's disease patients via morphological measures across three languages.

Embodied cognition research on Parkinson's disease (PD) points to disruptions of frontostriatal language functions as sensitive targets for clinical assessment. However, no existing approach has been tested for crosslinguistic validity, let alone by combining naturalistic tasks with machine-learning tools. To address these issues, we conducted the first classifier-based examination of morphological processing (a core frontostriatal function) in spontaneous monologues from PD patients across three typologically different languages.

Moebius syndrome: Craniofacial clinical manifestations and their association with prenatal exposure to misoprostol.

Background: A growing link between prenatal exposure to misoprostol (PEM) and Moebius syndrome (MS) or sequence has been reported. Our objectives were to describe the craniofacial clinical manifestations associated with MS and to determine the frequency of PEM, comparing cases of exposure and nonexposure.

Methods: A descriptive, cross-sectional study of 140 patients with MS.

In silico discovery and biological validation of ligands of FAD synthase, a promising new antimicrobial target.

New treatments for diseases caused by antimicrobial-resistant microorganisms can be developed by identifying unexplored therapeutic targets and by designing efficient drug screening protocols. In this study, we have screened a library of compounds to find ligands for the flavin-adenine dinucleotide synthase (FADS) -a potential target for drug design against tuberculosis and pneumonia- by implementing a new and efficient virtual screening protocol. The protocol has been developed for the in silico search of ligands of unexplored therapeutic targets, for which limited information about ligands or ligand-receptor structures is available.

Validation tests for cryo-EM maps using an independent particle set.

Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by providing 3D density maps of biomolecules at near-atomic resolution. However, map validation is still an open issue. Despite several efforts from the community, it is possible to overfit 3D maps to noisy data.

Flexi-pharma: a molecule-ranking strategy for virtual screening using pharmacophores from ligand-free conformational ensembles.

Computer-aided strategies are useful for reducing the costs and increasing the success-rate in drug discovery. Among these strategies, methods based on pharmacophores (an ensemble of electronic and steric features representing the target active site) are efficient to implement over large compound libraries. However, traditional pharmacophore-based methods require knowledge of active compounds or ligand-receptor structures, and only few ones account for target flexibility.

Cannabinoid CP55940 selectively induces apoptosis in Jurkat cells and in ex vivo T-cell acute lymphoblastic leukemia through HO signaling mechanism.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous malignant hematological disorder arising from T-cell progenitors. This study was aimed to evaluate the cytotoxic effect of CP55940 on human peripheral blood lymphocytes (PBL) and on T-ALL cells (Jurkat). PBL and Jurkat cells were treated with CP55940 (0-20 μM), and morphological changes in the cell nucleus/ DNA, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species levels were determined by fluorescence microscopy and flow cytometry.