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BACKGROUND: Serum albumin is the most abundant protein in the Mammalia blood plasma at where plays a decisive role in the transport wide variety of hydrophobic ligands. BSA undergoes oxidative modifications like the carbonylation by the reactive carbonyl species (RCSs) 4-hydroxy-2-nonenal (HNE), 4 hydroxy-2-hexenal (HHE), malondialdehyde (MDA) and 4-oxo-2-nonenal (ONE), among others. The structural and functional changes induced by protein carbonylation have been associated with the advancement of neurodegenerative, cardiovascular, metabolic and cancer diseases. METHODS: To elucidate structural effects of protein carbonylation with RCSs on BSA, parameters for six new non-standard amino acids were designated and molecular dynamics simulations of its mono­carbonylated-BSA systems were conducted in the AMBER force field. Trajectories were evaluated by RMSD, RMSF, PCA, RoG and SASA analysis. RESULTS: An increase in the conformational instability for all proteins modified with local changes were observed, without significant changes on the BSA global three-dimensional folding. A more relaxed compaction level and major solvent accessible surface area for modified systems was found. Four regions of high molecular fluctuation were identified in all modified systems, being the subdomains IA and IIIB those with the most remarkable local conformational changes. Regarding essential modes of domain movements, it was evidenced that the most representatives were those related to IA subdomain, while IIIB subdomain presented discrete changes. CONCLUSIONS: RCSs induces local structural changes on mono­carbonylated BSA. Also, this study extends our knowledge on how carbonylation by RCSs induce structural effects on proteins.

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Introducción: Los medicamentos de venta libre (OTC por su sigla en inglés Over The Counter), son ampliamente usados por la mayoría de las personas a nivel mundial, sin embargo, solamente son usados de forma responsable en países donde existe una farmacia comunitaria profesional legalizada. Objetivo: Describir los hábitos de consumo de medicamentos de venta libre por estudiantes universitarios del área de la salud. Materiales y métodos: Estudio descriptivo transversal, desarrollado en tres universidades de Cartagena. Se aplicó un instrumento tipo encuesta a 140 estudiantes acerca de hábitos de consumo y conocimiento sobre OTC, creencias, actitudes y prácticas. Resultados: El cuestionario presentó una consistencia interna alta con Alfa de Cronbach'sde 0,77. El 59% fueron mujeres, las en edades entre 16-30 años, el 91% estuvo de acuerdo que la automedicación es perjudicial. Sin embargo, 61% asegura automedicarse porque los padecimientos son menores y frecuentes. Los medicamentos de mayor consumo, fueron el acetaminofén 52,9% y los medicamentos antiinflamatorios no esteroides (AINES) con 16,48%, incluyeron en sus respuestas medicamentos de no venta libre. Conclusión: Los estudiantes son conscientes del riesgo de la automedicación, sin embargo, la practican de forma frecuente. Muchos reportaron consumo de medicamentos como amitriptilina, antibióticos, opiáceos, furosemida y corticoides.

Introduction: Over-the-counter (OTC) medications are widely used worldwide, however they are responsibly used only in countries with legalized professional community pharmacies. Objective:To describe over-the-counter medication use habits in university students from health programs. Materials and methods:Descriptive cross-sectional study carried out in three universities from Cartagena. A survey-type instrument was applied to 140 students, asking about their use habits and knowledge regarding OTC, beliefs, attitudes and practices. Results:The questionnaire showed a high internal inconsistency, with a Cronbach's alpha of 0.77. 59% of participants were women aged between 16 to 30 years old and 91% agreed that self-medication is harmful. Nevertheless, 61% self-medicated because of minor and frequent conditions. OTC medications with the highest use were acetaminophen (52.9%) and NSAIDs (16.48%). Conclusions:Even though students are aware of the self-medication risks, they still practice it frequently. Many participants reported the use of medications such as amitriptyline, antibiotics, opioids, furosemide, and corticosteroids.

Introdução:Os medicamentos isentos de prescrição (OTCOver The Counter) são amplamente utilizados pela maioria das pessoas em todo o mundo, porém somente são usados de forma responsável em países onde existe uma farmácia comunitária profissional legalizada. Objetivo: Descrever os hábitos de consumo de medicamentos isentos de prescrição por universitários da área da saúde. Materiais e métodos: Estudo descritivo transversal, desenvolvido em três universidades de Cartagena. Foi aplicado um instrumento do tipo inquérito a 140 alunos sobre hábitos de consumo e conhecimentos sobre OTC, crenças, atitudes e práticas. Resultados: O questionário apresentou alta consistência interna com Alfa de Cronbach ́sde 0,77. 59% eram mulheres, com idades entre 16 e 30 anos, 91% concordaram que a automedicação é prejudicial. No entanto, 61% dizem que se automedicam porque os males são leves e frequentes. Os medicamentos de maior consumo foram o acetaminofeno 52,9% e os anti-inflamatórios não esteroidais com 16,48%, incluindo medicamentos isentos de prescrição em suas respostas. Conclusão: Os alunos estão cientes do risco da automedicação, porém isto é praticado com frequência. Muitos relataram consumo de medicamentos como amitriptilina, antibióticos, opioides, furosemida e corticosteroides.

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The emergence of the new SARS-CoV-2 virus, which causes the disease known as COVID-19, has generated a pandemic that has plunged the world into a health crisis. The infection process is triggered by the direct binding of the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) of the host cell. In the present study, virtual screening techniques such as molecular docking, molecular dynamics, calculation of free energy using the GBSA method, prediction of drug similarity, pharmacokinetic, and toxicological properties of various ligands interacting with the RBD-ACE2 complex were applied. The ligands radotinib, hinokiflavone, and ginkgetin were identified as potential destabilizers of the RBD-ACE2 interaction, which could produce their pharmacological effect by interacting at an allosteric site of ACE2, with affinity energy values of -10.2 ± 0.1, -9.8 ± 0.0, and -9.4 ± 0.0 kcal/mol, indicating strong receptor affinity. The complex with hinokiflavone showed the highest conformational stability and rigidity of the dynamic simulation and also obtained the best binding free energy of the three molecules, with an energy of -215.86 kcal/mol.

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Introducción: en general, el orégano es una planta medicinal usada en los pueblos de la costa Caribe colombiana para tratar afecciones del aparato respiratorio y el oído externo debido a su potencial efecto antiinflamatorio, analgésico y antiséptico; sin embargo, esto no se ha validado mediante ensayos clínicos. Objetivo: realizar un cribado virtual basado en el acoplamiento molecular de metabolitos secundarios identificados en el Origanum vulgare y mejorana frente al receptor Nav1.7 para evaluar el potencial efecto anestésico a nivel del oído externo. Método: el presente es un estudio in silico con un enfoque de cribado virtual por acoplamiento molecular, para lo cual se usó el software AutoDock Vina y para las predicciones farmacocinéticas se usó la herramienta en línea SwissADME del Swiss Institute of Bioinformatics (http://www.sib.swiss). Adicionalmente, se evaluó la toxicidad in silico de las moléculas utilizando el servidor GUSAR-Online. Resultados: de las 99 moléculas que fueron evaluadas por acoplamiento molecular se evidenció que las mayores afinidades con respecto al canal Nav1.7 fueron el ácido clorogénico, la rutina, la luteolina, el luteosido y la apigenina, donde se presentaron energías de afinidad con el sitio de unión en el poro central del canal a valores entre -5,40 ± 0,00 a -5,57 ± 0,06 kcal/mol; de estos, de acuerdo con el análisis ADMET y GUSAR, solo el ácido clorogénico, la luteolina y la apigenina son buenos candidatos potenciales para fármacos anestésicos ya que cumplen con las cinco reglas de Lipinski. Conclusión: con base en los estudios fitoquímicos de O. vulgare y mejorana que han reportado los metabolitos secundarios presentes en los extractos de estas plantas, se evidenció en el presente estudio in silico su acoplamiento al canal Nav1.7 expresado en la vía neurosensitiva del oído. Se demostró, además, que el ácido clorogénico, la luteolina y la apigenina podrían ser potenciales fármacos anestésicos locales para las afecciones del oído.

Introduction: In general, oregano is a medicinal plant used in rural areas of the colombian Caribbean coast to treat conditions of the respiratory system and external ear due to its potential anti-inflammatory, analgesic and antiseptic effect, however, it has not been validated through clinical trials. Objective: To carry out a virtual screening based on molecular coupling of secondary metabolites identified in Origanum vulgare and marjoram against the Nav1.7 receptor to evaluate the potential anesthetic effect at the level of the external ear. Method: This is an in-silico study with a virtual molecular docking screening approach, for which the AutoDock Vina software was used and the Swiss Institute of Bioinformatics (http://www.sib.swiss) online tool SwissADME was used for pharmacokinetic predictions. Additionally, the in-silico toxicity of the molecules was evaluated using the GUSAR-Online server. Results: Of the 99 molecules that were evaluated by molecular coupling, it was shown that the highest affinities with respect to the Nav1.7 channel were chlorogenic acid, rutin, luteolin, luteoside and apigenin, where affinity energies were presented with the binding site in the central pore of the channel at values between -5.40 ± 0.00 to -5.57 ± 0.06 kcal/mol, which according to the ADMET and GUSAR analysis, only chlorogenic acid, luteolin and apigenin are good potential candidates for anesthetic drugs complying with the 5 rules of Lipinsky. Conclusion: Based on the phytochemical studies of O. vulgare and marjoram that have reported the secondary metabolites present in the extracts of these plants, their coupling to the Nav1.7 channel expressed in the neurosensory pathway of the ear was evidenced in this in-silico study. It was also shown that chlorogenic acid, luteolin and apigenin could be potential local anesthetic drugs for ear conditions.

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INTRODUCTION: Leukoplakia is one of the most frequently found lesions in the oral cavity, with a probability of 17 to 24% of becoming malignant cells in a period of 30 years. OBJECTIVE: To identify differentially expressed gene profiles of leukoplakia and its progression to oral squamous cell carcinoma, essential for the discovery of new biomarkers to predict and prevent the presence of diseases in the oral cavity. METHODS: Initially, gene profiles of GSE85514 and GSE160042 from the Gene Expression Omnibus database were used. Differentially expressed genes were identified using GEO2R. The CLUEGO plugin in Cytoscape was used for DEG functionality and enrichment analysis. Finally, a protein-protein interaction (PPI) network was constructed using Cytoscape from data collected online from the STRING server. RESULTS: According to the MCC algorithm, the 10 most found gene sequences were HNRNPU, SMC1A, PAFAH1B1, EHMT1, SPTBN4, OLFM1, NCAM1, SF3B3, FGF2, and UBE2I; with HNRNPU, SMC1A, and PAFAH1B1 being the most representative of the modules. CONCLUSIONS: We were able to describe the gene sequences that promote the progression from leukoplakia to oral squamous cell carcinoma. Within these genes, the HNRNPU, SMC1A, and PAFAH1B1 constitute the main promising therapeutic targets to counteract the progression of oral cancer, they could also be important biomarkers for the diagnosis and classification of the disease.

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The data described here supports a part of the research article "Effect of 4­HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with ß­Spectrin: A Molecular Dynamics Simulation Study" [1]. Dataset on Gaff force field parameters of AMBER is provided for the non-standard arginine resulting of reaction with 4-hydroxy-2-nonenal (4-HNE), the major secondary product of lipids peroxidation. Arg-HNE 2-pentilpyrrole adduct is part of the 4-hydroxyalkenals described in various physiopathological disorders related to increased oxidative stress. Data include a framework for derivation of missing bonds, angles and dihedral parameters for modified arginine, alongside optimized partial charges derived with Restrained Electrostatic Potential (RESP) method and the new force field parameters obtained by quantum mechanicals methods (QM) using Hartree-Fock (HF)/6 - 31G** level of theory. Benchmark as a graphics tutorial summary steps to obtained new parameters and the validation of non-standard amino acids is presented. The new residue constructed is put available to the scientific community to perform molecular dynamics simulations of modified 4-HNE proteins on arginine residue and complete the set of data parameters for nucleophilic residues with this reactive aldehyde ADDIN EN.CITE ADDIN EN.CITE.DATA [2]. Data that could be used for the researchers interested in the role of protein oxidation as mediator in cellular pathophysiological.

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4-HNE-modified ankyrins have been described in diseases such as diabetes, renal failure, G6PD deficient, sickle cell trait, and P. falciparum infected erythrocytes with different AB0 blood groups. However, effects at the atomic level of this carbonylation on structure and function of modified protein are not yet fully understood. We present a study based on molecular dynamics simulations of nine 4-HNE modified residues of the ZU5-ANK ankyrin domain with ß-spectrin and their binding energy profiles. Results show that 4-HNE induced local conformational changes over all protein systems evaluated, increased mobility in the modification sites, and localized structural changes between the positively charged patch of the ZU5-ANK domain. Carbonylation with 4-HNE on lysine residues decreased the affinity between ZU5-ANK and the 14-ß-spectrin repeat by reducing electrostatic and van der Waals interactions. The presented work provides further insight into understanding the loss of human erythrocyte deformation capacity under conditions of oxidative stress in different diseases.

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4-hydroxy-2-nonenal (4-HNE) is the main end product of peroxidation in lipids, capable of introduce carbonyl groups to nucleophilic amino acids via Michael additions and alter protein function. It has been reported that 4-HNE protein carbonylation is associated with intracellular protein aggregation, the pathogenesis of neurodegenerative and metabolic diseases and yet it is unclear how the carbonylation affects the protein structure and dynamics at the atomic level. Here, we analysis the structural effects of 4-HNE modification through formation of Michael adducts of Cys-4HNE, His-4HNE and Lys-4HNE on Serum Albumin (BSA) and Thioredoxin (TRX). Since both proteins have experimental evidence to possess 4-HNE-modifications on cysteine, histidine and lysine residues, extended molecular dynamics simulations were performed with AMBER to study the carbonylation effects in the structure of these proteins. BSA is the main protein of plasma while TRX is an important antioxidant enzyme. Results showed local changes and alteration in the conformational stability, folding and flexibility after including the 4-HNE modification. DSSP analysis showed important structural modifications as a consequence of the inclusion of the modified residues. Analysis of the computed trajectories suggests that 4-HNE decreases stability, increases local flexibility and produced modest unfolding on both tested proteins. Finally, all the systems evaluated shown an increase in the lipophilic potential and a modest decrease in the electrostatic potential in BSA but an increase in TRX.

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Resumen Introducción. Dada la alta prevalencia de la infección del tracto urinario (ITU) y la significativa resistencia de los patógenos implicados, el mundo se enfrenta a un problema creciente de salud pública. Objetivos. Describir la prevalencia de ITU y uropatógenos y analizar los perfiles de susceptibilidad en los reportes de urocultivos del laboratorio de microbiología de un hospital de referencia. Materiales y métodos. Se llevó a cabo un estudio transversal con una muestra de 396 urocultivos positivos en el que se calculó la prevalencia de ITU, uropatógenos y perfil de resistencia microbiana. Se realizaron pruebas de hipótesis y regresión logística no condicional para conocer si existía diferencia estadística entre el género. Resultados. La prevalencia de ITU fue del 28%, los tres patógenos aislados más frecuentes fueron Escherichia coli, Escherichia. coli con β-lactamasas de espectro extendido y Pseudomonas. aeruginosa. La mayor frecuencia de resistencia a antibióticos para estos patógenos fue ampicilina (66.6%), ceftriaxona (100%) y gentamicina (39.5%), respectivamente. Conclusiones. Por la alta prevalencia, el amplio espectro de uropatógenos aislados y la diversidad de perfiles de resistencia antibiótica, se evidencia la necesidad de desarrollar investigaciones locales que permitan orientar las acciones en salud y vigilancia epidemiológica.

Abstract Introduction: Given the high prevalence of urinary tract infection (UTI) and the significant resistance of the pathogens involved, the world faces a growing public health issue. More studies are needed to analyze microbial susceptibility profiles. Objectives: To describe the prevalence of UTIs and uropathogens and to analyze the susceptibility profiles of urine samples of the microbiology laboratory of a reference hospital. Materials and methods: A cross-sectional study was carried out with a sample of 396 positive urine cultures, in which the prevalence of UTIs, uropathogens and microbial resistance profile was estimated. Hypothesis tests and non-conditional logistic regression tests were performed to know if there was a statistical difference between genders. Results: The prevalence of UTIs was 28%. The three most frequent isolated pathogens were Escherichia coli, Escherichia coli with extended-spectrum β-lactamases and Pseudomonas aeruginosa. The highest frequency of antibiotics resistance for these pathogens was ampicillin (66.6%), ceftriaxone (100%) and gentamicin (39.5%), respectively. Conclusions: Their high prevalence, the broad spectrum of isolated uropathogens and the diversity of antibiotic resistance profiles make evident the need to develop local research to guide health actions and epidemiological surveillance.

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The data described here support the research article "4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study" (Alviz-Amador et al., 2018) . Dataset on Gaff force field parameters of AMBER is provided for assembled three non-standard amino acids resulting of the 4-HNE Michael addition, the main end product of lipids peroxidation. Data include a framework for derivation of missing bonds, angles and dihedral parameters for Cys, His, and Lys modified amino acids, alongside optimized partial charges derived with Restrained Electrostatic Potential (RESP) method and the new force field parameters obtained by quantic mechanical (QM) using HF/6-31G** level of theory. Benchmark as a graphics tutorial summary steps to obtained new parameters and the validation of non-standard amino acids is presented. The new residues constructed are put available to the scientific community to perform molecular dynamics simulations of modified 4-HNE proteins.