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1.
BMC Oral Health ; 24(1): 928, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127650

RESUMEN

INTRODUCTION: Edentulism is the partial or total loss of teeth, it is irreversible and disabling due to its sequelae in the masticatory, phonetic and aesthetic function that affect the quality of life. OBJECTIVE: To establish the impact of edentulism and sociodemographic factors on the quality of life of the Salvadoran population. MATERIALS AND METHODS: Secondary cross-sectional analysis of data in 3322 users of the Public Health System of El Salvador, aged 15 to > 60 years. The variables under study were sociodemographic, edentulismo and quality of life. Edentulism was determined by clinical examination using the Oral Impact on Daily Performance scale. The statistical analysis was performed using χ2, OR, multiple regression analysis and set the significance threshold at p < 0.05. RESULTS: Partial edentulism in the upper jaw was present in 68.24% people, partial edentulism in the lower jaw was present in 72.42% people and complete edentulism was observed in 2.02% people. There were significant sex differences and a relationship between sex and quality of life (p < 0.004); the self-perception of severe/very severe impacts was greater in women. People without education or with primary or secondary education only were the most affected (p < 0.05). Tooth loss increases with age, affecting quality of life in a severe/very severe manner. Complete edentulism had greater impacts on quality of life in terms of eating (25.64%), speaking (21.15%), and socializing/enjoying contact with people (10.90%). A severe/very severe impact on quality of life of teeth lost was reported mainly by those over 60 years of age, with an average of 11 missing posterior teeth, 6 missing anterior teeth and 13 missing teeth per patient. Those missing up to 6 anterior teeth were times more likely to perceive severe/very severe impacts on quality of life than those without any missing teeth (OR:5.788). Edentulism affected the quality of life of those examined, especially the loss of upper anterior teeth.


Asunto(s)
Calidad de Vida , Humanos , Estudios Transversales , Femenino , Masculino , Persona de Mediana Edad , Adulto , Adolescente , Adulto Joven , El Salvador , Factores Sexuales , Escolaridad , Boca Edéntula/epidemiología , Boca Edéntula/psicología , Anciano
2.
Entropy (Basel) ; 26(8)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39202116

RESUMEN

This paper proposes an advancement in the application of a Technical Vision System (TVS), which integrates a laser scanning mechanism with a single light sensor to measure 3D spatial coordinates. In this application, the system is used to scan and digitalize objects using a rotating table to explore the potential of the system for 3D scanning at reduced resolutions. The experiments undertaken searched for optimal scanning windows and used statistical data filtering techniques and regression models to find a method to generate a 3D scan that was still recognizable with the least amount of 3D points, balancing the number of points scanned and time, while at the same time reducing effects caused by the particularities of the TVS, such as noise and entropy in the form of natural distortion in the resulting scans. The evaluation of the experimentation results uses 3D point registration methods, joining multiple faces from the original volume scanned by the TVS and aligning it to the ground truth model point clouds, which are based on a commercial 3D camera to verify that the reconstructed 3D model retains substantial detail from the original object. This research finds it is possible to reconstruct sufficiently detailed 3D models obtained from the TVS, which contain coarsely scanned data or scans that initially lack high definition or are too noisy.

3.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38674160

RESUMEN

Slc4a genes encode various types of transporters, including Na+-HCO3- cotransporters, Cl-/HCO3- exchangers, or Na+-driven Cl-/HCO3- exchangers. Previous research has revealed that Slc4a9 (Ae4) functions as a Cl-/HCO3- exchanger, which can be driven by either Na+ or K+, prompting investigation into whether other Slc4a members facilitate cation-dependent anion transport. In the present study, we show that either Na+ or K+ drive Cl-/HCO3- exchanger activity in cells overexpressing Slc4a8 or Slc4a10. Further characterization of cation-driven Cl-/HCO3- exchange demonstrated that Slc4a8 and Slc4a10 also mediate Cl- and HCO3--dependent K+ transport. Full-atom molecular dynamics simulation on the recently solved structure of Slc4a8 supports the coordination of K+ at the Na+ binding site in S1. Sequence analysis shows that the critical residues coordinating monovalent cations are conserved among mouse Slc4a8 and Slc4a10 proteins. Together, our results suggest that Slc4a8 and Slc4a10 might transport K+ in the same direction as HCO3- ions in a similar fashion to that described for Na+ transport in the rat Slc4a8 structure.


Asunto(s)
Potasio , Simportadores de Sodio-Bicarbonato , Animales , Ratones , Bicarbonatos/metabolismo , Sitios de Unión , Antiportadores de Cloruro-Bicarbonato/metabolismo , Antiportadores de Cloruro-Bicarbonato/genética , Cloruros/metabolismo , Transporte Iónico , Simulación de Dinámica Molecular , Potasio/metabolismo , Sodio/metabolismo , Simportadores de Sodio-Bicarbonato/metabolismo , Simportadores de Sodio-Bicarbonato/genética
4.
Mar Pollut Bull ; 200: 116092, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38359479

RESUMEN

Due to the amply exposure of marine turtles to marine plastic pollution, this is a reason that the green sea turtle Chelonia mydas makes a good candidate species as a bioindicator for plastic pollution. Turtle feces were collected at Isla Blanca on the northeast Caribbean coast of the Yucatan Peninsula, Mexico. Microplastic extraction was done following Hidalgo-Ruz et al. (2012) and Masura et al. (2015) methods. After organic matter degradation of the feces samples, microplastics were identified and quantified by stereomicroscope. Their morphostructure was analyzed by scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy, while their composition was determined by Fourier transform infrared spectroscopy and Raman spectroscopy. Microplastics (MP) abundance ranged from 10 ± 2 MP·g-1 to 89 ± 3 MP·g-1. Kruskal Wallis test (KW = 70.31, p < 0.001) showed a significant difference between 22 green turtles analyzed. Most of the microplastics were fiber type. Blue, purple, and transparent fibers were the most abundant. The identified microplastics were nylon (polyamide), PVC, polypropylene, polyester, and viscose (cellulose). The non-invasive method used here allowed the detection of microplastic pollution and is promising for long-term microplastic pollution monitoring.


Asunto(s)
Tortugas , Contaminantes Químicos del Agua , Animales , Microplásticos , Plásticos/química , México , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente/métodos , Región del Caribe , Nylons
5.
Int J Mol Sci ; 24(22)2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-38003447

RESUMEN

Acute ST-elevation myocardial infarction (STEMI) leads to myocardial injury or necrosis, and M1 macrophages play an important role in the inflammatory response. Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are capable of modulating macrophage plasticity, principally due to their immunoregulatory capacity. In the present study, we analyzed the capacity of MSCs to modulate macrophages derived from monocytes from patients with STEMI. We analyzed the circulating levels of cytokines associated with M1 and M2 macrophages in patients with STEMI, and the levels of cytokines associated with M1 macrophages were significantly higher in patients with STEMI than in controls. BM-MSCs facilitate the generation of M1 and M2 macrophages. M1 macrophages cocultured with MSCs did not have decreased M1 marker expression, but these macrophages had an increased expression of markers of the M2 macrophage phenotype (CD14, CD163 and CD206) and IL-10 and IL-1Ra signaling-induced regulatory T cells (Tregs). M2 macrophages from patients with STEMI had an increased expression of M2 phenotypic markers in coculture with BM-MSCs, as well as an increased secretion of anti-inflammatory cytokines and an increased generation of Tregs. The findings in this study indicate that BM-MSCs have the ability to modulate the M1 macrophage response, which could improve cardiac tissue damage in patients with STEMI.


Asunto(s)
Células Madre Mesenquimatosas , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Fenotipo , Células Madre Mesenquimatosas/metabolismo
6.
Cureus ; 15(10): e46524, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37927772

RESUMEN

BACKGROUND AND OBJECTIVES: This study aimed to identify the relationship between prevention measures and protective barriers in dental practice in El Salvador and Mexico during the COVID-19 pandemic in 2020 and 2021. MATERIALS AND METHODS: A longitudinal study was conducted from June 2020 to December 2021, involving 1,719 dentists divided into four groups based on location and year. A 20-question survey in Spanish was utilized and validated with a Cronbach's alpha value of 0.84. RESULTS: The use of phone triage (OR = 1.3), thermometers (OR = 1.4), physical distancing (OR = 1.7), and face shields (OR = 2.6) was significantly associated with dental practice in both countries during the pandemic. CONCLUSIONS: During 2020 and 2021, dental care in El Salvador and Mexico was significantly linked to COVID-19 preventive measures. Phone triage, thermometers, distancing, and face shields positively correlated with dental services. National health agencies should promote the use of minimum preventive measures in dental care, preparing for potential reinfections or new pandemics from emerging virus variants.

7.
Entropy (Basel) ; 25(8)2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37628237

RESUMEN

A novelty signal processing method is proposed for a technical vision system (TVS). During data acquisition of an optoelectrical signal, part of this is random electrical fluctuation of voltages. Information theory (IT) is a well-known field that deals with random processes. A method based on using of the Shannon Entropy for feature extractions of optical patterns is presented. IT is implemented in structural health monitoring (SHM) to augment the accuracy of optoelectronic signal classifiers for a metrology subsystem of the TVS. To enhance the TVS spatial coordinate measurement performance at real operation conditions with electrical and optical noisy environments to estimate structural displacement better and evaluate its health for a better estimation of structural displacement and the evaluation of its health. Five different machine learning (ML) techniques are used in this work to classify optical patterns captured with the TVS. Linear predictive coding (LPC) and Autocorrelation function (ACC) are for extraction of optical patterns. The Shannon entropy segmentation (SH) method extracts relevant information from optical patterns, and the model's performance can be improved. The results reveal that segmentation with Shannon's entropy can achieve over 95.33%. Without Shannon's entropy, the worst accuracy was 33.33%.

8.
BMC Psychol ; 11(1): 115, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37060098

RESUMEN

BACKGROUND: The global spread of COVID-19 forced schools at all educational levels to close, which was repeated in more than 60 countries. In addition, the COVID-19 pandemic has affected the mental health of dental students world wide. This study hypothesizes that the prevalence of depression in dental students from El Salvador is higher than that reported in studies from Europe, Asia, and North America. METHODS: This study was an online cross-sectional survey performed at the Faculty of Dentistry of the University of Salvador. The PHQ-9 questionnaire was applied to know the level of depression of the students, and a questionnaire focused on learning the opinion of the students on the hybrid teaching model adopted. Approximately 450 students participated in both questionnaires. RESULTS: Regarding the levels of depression present in the students, 14% had minimal depression, 29% had medium depression, 23% had moderate depression and, 34% had severe depression. The students had an excellent opinion regarding the hybrid learning model. CONCLUSIONS: The prevalence of depression in dental students in El Salvador seems to be higher than that reported in studies in non-Latin American countries. Therefore, universities must generate care plans for mental health to avoid these harmful effects on students during future contingencies.


Asunto(s)
COVID-19 , Pandemias , Humanos , Estudios Transversales , Estudiantes de Odontología , COVID-19/epidemiología , Aprendizaje , Universidades
9.
Int J Mol Sci ; 24(5)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36901904

RESUMEN

TRPV5 and TRPV6 are calcium-selective ion channels expressed at the apical membrane of epithelial cells. Important for systemic calcium (Ca2+) homeostasis, these channels are considered gatekeepers of this cation transcellular transport. Intracellular Ca2+ exerts a negative control over the activity of these channels by promoting inactivation. TRPV5 and TRPV6 inactivation has been divided into fast and slow phases based on their kinetics. While slow inactivation is common to both channels, fast inactivation is characteristic of TRPV6. It has been proposed that the fast phase depends on Ca2+ binding and that the slow phase depends on the binding of the Ca2+/Calmodulin complex to the internal gate of the channels. Here, by means of structural analyses, site-directed mutagenesis, electrophysiology, and molecular dynamic simulations, we identified a specific set of amino acids and interactions that determine the inactivation kinetics of mammalian TRPV5 and TRPV6 channels. We propose that the association between the intracellular helix-loop-helix (HLH) domain and the TRP domain helix (TDh) favors the faster inactivation kinetics observed in mammalian TRPV6 channels.


Asunto(s)
Calcio , Canales Catiónicos TRPV , Animales , Calcio/metabolismo , Canales de Calcio/metabolismo , Células Epiteliales/metabolismo , Secuencias Hélice-Asa-Hélice , Mamíferos/metabolismo , Canales Catiónicos TRPV/metabolismo , Humanos
10.
Pathogens ; 12(2)2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36839522

RESUMEN

The increasing detection of Porcine circovirus 3 (PCV3, family Circoviridae) in clinically ill pigs worldwide has raised concerns on the implications of the virus on porcine health and the pork industry. Although pork production constitutes an important component of the livestock economy and is a major source of animal protein in the Caribbean Islands, there are no reports on PCV3 in pigs from the region so far. In the present study, PCV3 was detected in 21% (21/100) of diarrheic pigs (sampled at three farms) from the Caribbean nation of the Dominican Republic (DR). Although the sample size varied between porcine age groups, the highest PCV3 detection rates (35.3% each, respectively) were observed in piglets and growers. Co-infections with PCV2 and porcine adenovirus were observed in 38.09% and 9.52% of the PCV3 positive samples, respectively. The complete genomes of 11 DR PCV3 strains were analyzed in the present study, revealing a unique deletion (corresponding to nucleotide residue at position 1165 of reference PCV3 sequences) in one of the DR PCV3 sequences. Based on sequence identities and phylogenetic analysis (open reading frame 2 and complete genome sequences), the DR PCV3 strains were assigned to genotype PCV3a, and shared high sequence homologies (>98% identities) between themselves and with those of other PCV3a (Clade-1) strains, corroborating previous observations on the genetic stability of PCV3 worldwide. To our knowledge, this is the first report on the detection and molecular characterization of PCV3 in pigs from the Caribbean region, providing important insights into the expanding global distribution of the virus, even in isolated geographical regions (the Island of Hispaniola). Our findings warrant further investigations on the molecular epidemiology and economic implications of PCV3 in pigs with diarrhea and other clinical conditions across the Caribbean region.

11.
Artículo en Español | LILACS, CUMED | ID: biblio-1530105

RESUMEN

Introducción: La vacuna antialérgica de segunda generación PROLINEM-DS está compuesta por alérgenos del ácaro Dermatophagoides siboney y la combinación de adyuvantes: proteoliposoma de N. meningitidis B y gel de hidróxido de aluminio. La adsorción del alérgeno es relevante para la seguridad y eficacia clínica de las vacunas adsorbidas en gel de hidróxido de aluminio en estudios previos se demostró la influencia negativa de los iones fosfato en la adsorción del alérgeno. Objetivo: Evaluar la inmunogenicidad y capacidad protectora de cuatro variantes de formulación obtenidas dentro del espacio de diseño de la vacuna PROLINEM DS. Métodos: Se emplearon 4 variantes de formulación con diferentes contenidos de tampón fosfato salino y gel de hidróxido de aluminio. Se administraron a ratones BALB/c 3 dosis subcutáneas una por semana. Luego, los ratones fueron sometidos a reto alergénico por aerosol. Resultados: Todas las variantes indujeron anticuerpos IgG1 e IgG2a alérgeno específico. Este efecto se correlacionó con el balance de citoquinas proinflamatorias Th1/Th2 en los pulmones y en los ganglios. La variante con reducción de tampón fosfato salino y gel de hidróxido de aluminio fue la de mayor índice IgG/IgE después de la vacunación. Esta relación muestra, en una variable, el equilibrio entre los componentes potencialmente bloqueadores y efectores. La tolerancia local en el lugar de la inyección mostró una reducción de los granulomas en los ratones vacunados con menos gel de hidróxido de aluminio. Conclusiones: La reducción del contenido de gel de hidróxido de aluminio y fosfatos se consideran mejoras farmacéuticas sin inconvenientes en cuanto a la inmunogenicidad de esta vacuna con un perfil de seguridad satisfactorio para futuros ensayos clínicos en humanos.


Introduction: The second generation anti allergic vaccine named PROLINEM DS is based on allergens from D. siboney house dust mite and a combination adjuvant containing PL and Alum. Allergen adsorption is relevant both safety and clinical efficacy in alum-adsorbed vaccines. Negative influence of phosphate ions on allergen adsorption was demonstrated in previous researches. Objective: To evaluate immunogenicity and protective efficacy of four variants obtained within design space of PROLINEM DS vaccine. Methods: Four variants were differentiated from each other by both phosphate and alum contents. Balb/c mice were administered with 3 doses by subcutaneous route. Further, mice were subjected to allergen aerosol challenge. Results: Specific IgG1 and IgG2a antibodies were induced by four vaccine variants. It was correlated with pro inflammatory cytokines balance Th1/Th2 both in lungs and lymphatic nodes. Formulation with lower PBS and Alum levels showed the highest IgG/IgE ratio at the end of vaccination schedule. This ratio shows in one variable the balance between potentially blocking and effector components. Mice injected with lower level of Alum showed a reduction of granuloma size in the site of vaccine administration. Conclusion: Decrease both alum and phosphate contents were a pharmaceutical improvement for antiallergic vaccines formulation. Safety and efficacy in this vaccine are crucial for future human clinical trials.


Asunto(s)
Humanos
13.
J Med Chem ; 65(22): 15014-15027, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36378530

RESUMEN

Chemical structures of selective blockers of TASK channels contain aromatic groups and amide bonds. Using this rationale, we designed and synthesized a series of compounds based on 3-benzamidobenzoic acid. These compounds block TASK-1 channels by binding to the central cavity. The most active compound is 3-benzoylamino-N-(2-ethyl-phenyl)-benzamide or F3, blocking TASK-1 with an IC50 of 148 nM, showing a reduced inhibition of TASK-3 channels and not a significant effect on different K+ channels. We identified putative F3-binding sites in the TASK-1 channel by molecular modeling studies. Mutation of seven residues to A (I118A, L122A, F125A, Q126A, L232A, I235A, and L239A) markedly decreased the F3-induced inhibition of TASK-1 channels, consistent with the molecular modeling predictions. F3 blocks cell proliferation and viability in the MCF-7 cancer cell line but not in TASK-1 knockdown MCF-7 cells, indicating that it is acting in TASK-1 channels. These results indicated that TASK-1 is necessary to drive proliferation in the MCF-7 cancer cell line.


Asunto(s)
Neoplasias , Humanos , Relación Estructura-Actividad , Sitios de Unión , Proliferación Celular , Modelos Moleculares , Células MCF-7
14.
Viruses ; 14(8)2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-36016421

RESUMEN

We report here high rates (47.5%, 48/101) of detection of porcine circovirus 2 (PCV2) in diarrheic pigs from three pig farms in the Dominican Republic. Seventeen of the PCV2 positive samples, representing the three pig farms, different age groups and sampling periods (2020-2021), were amplified for the complete PCV2 genome. Based on analysis of open reading frame 2 and complete genome sequences, the 17 PCV2 strains were assigned to the PCV2d genotype. Significant differences were observed in PCV2 detection rates between the vaccinated (20% (10/50)) and unvaccinated (62.5% (10/16) and 80% (28/35)) farms, corroborating previous observations that PCV2a-based vaccines confer protection against heterologous PCV2 genotypes. The present study is the first to report detection and molecular characterization of PCV2 from the Dominican Republic, warranting large-scale molecular epidemiological studies on PCV2 in pig farms and backyard systems across the country. For the first time, PCV2d was identified as the predominant PCV2 genotype in a study from the Caribbean region, suggesting that a genotype shift from PCV2b to PCV2d might be happening in the Caribbean region, which mirrored the current PCV2 genotype scenario in many other parts of the world. Besides PCV2, we also identified a pigeon circovirus-like virus, and a circular Replication-associated protein (Rep)-encoding single-stranded (CRESS) DNA virus, which was characterized for the complete genome. The CRESS DNA virus shared a similar genomic organization and was related to unclassified CRESSV2 DNA viruses (belonging to the Order Cirlivirales) from porcine feces in Hungary, indicating that related unclassified CRESS DNA viruses are circulating among pigs in different geographical regions, warranting further studies on the epidemiology and biology of these novel viruses.


Asunto(s)
Brassicaceae , Infecciones por Circoviridae , Circovirus , Enfermedades de los Porcinos , Animales , Infecciones por Circoviridae/epidemiología , Infecciones por Circoviridae/veterinaria , Circovirus/genética , República Dominicana/epidemiología , Genotipo , Filogenia , Porcinos
15.
Onco Targets Ther ; 15: 783-797, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35899081

RESUMEN

Potassium (K+) channels are highly regulated membrane proteins that control the potassium ion flux and respond to different cellular stimuli. These ion channels are grouped into three major families, Kv (voltage-gated K+ channel), Kir (inwardly rectifying K+ channel) and K2P (two-pore K+ channels), according to the structure, to mediate the K+ currents. In cancer, alterations in K+ channel function can promote the acquisition of the so-called hallmarks of cancer - cell proliferation, resistance to apoptosis, metabolic changes, angiogenesis, and migratory capabilities - emerging as targets for the development of new therapeutic drugs. In this review, we focus our attention on the different K+ channels associated with the most relevant and prevalent cancer types. We summarize our knowledge about the potassium channels structure and function, their cancer dysregulated expression and discuss the K+ channels modulator and the strategies for designing new drugs.

16.
Pharmaceutics ; 14(7)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35890252

RESUMEN

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that a combined blockade of Nav1.5 (and its current, INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without alterations in ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD) as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We present a computational workflow for a flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of the flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the central cavity and consists of a hydrophobic patch and a polar region, involving residues from the S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.

17.
Biology (Basel) ; 11(8)2022 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-35892953

RESUMEN

Two pore domain potassium channels (K2P) are strongly expressed in the nervous system (CNS), where they play a central role in excitability. These channels give rise to background K+ currents, also known as IKSO (standing-outward potassium current). We detected the expression in primary cultured cerebellar granule neurons (CGNs) of TWIK-1 (K2P1), TASK-1 (K2P3), TASK-3 (K2P9), and TRESK (K2P18) channels by immunocytochemistry and their association with lipid rafts using the specific lipids raft markers flotillin-2 and caveolin-1. At the functional level, methyl-ß-cyclodextrin (MßCD, 5 mM) reduced IKSO currents by ~40% in CGN cells. To dissect out this effect, we heterologously expressed the human TWIK-1, TASK-1, TASK-3, and TRESK channels in HEK-293 cells. MßCD directly blocked TASK-1 and TASK-3 channels and the covalently concatenated heterodimer TASK-1/TASK-3 currents. Conversely, MßCD did not affect TWIK-1- and TRESK-mediated K+ currents. On the other hand, the cholesterol-depleting agent filipin III did not affect TASK-1/TASK-3 channels. Together, the results suggest that neuronal background K+ channels are associated to lipid raft environments whilst the functional activity is independent of the cholesterol membrane organization.

18.
Front Pharmacol ; 13: 855792, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370665

RESUMEN

The identification of similar three-dimensional (3D) amino acid patterns among different proteins might be helpful to explain the polypharmacological profile of many currently used drugs. Also, it would be a reasonable first step for the design of novel multitarget compounds. Most of the current computational tools employed for this aim are limited to the comparisons among known binding sites, and do not consider several additional important 3D patterns such as allosteric sites or other conserved motifs. In the present work, we introduce Geomfinder2.0, which is a new and improved version of our previously described algorithm for the deep exploration and discovery of similar and druggable 3D patterns. As compared with the original version, substantial improvements that have been incorporated to our software allow: (i) to compare quaternary structures, (ii) to deal with a list of pairs of structures, (iii) to know how druggable is the zone where similar 3D patterns are detected and (iv) to significantly reduce the execution time. Thus, the new algorithm achieves up to 353x speedup as compared to the previous sequential version, allowing the exploration of a significant number of quaternary structures in a reasonable time. In order to illustrate the potential of the updated Geomfinder version, we show a case of use in which similar 3D patterns were detected in the cardiac ions channels NaV1.5 and TASK-1. These channels are quite different in terms of structure, sequence and function and both have been regarded as important targets for drugs aimed at treating atrial fibrillation. Finally, we describe the in vitro effects of tafluprost (a drug currently used to treat glaucoma, which was identified as a novel putative ligand of NaV1.5 and TASK-1) upon both ion channels' activity and discuss its possible repositioning as a novel antiarrhythmic drug.

19.
Matern Child Nutr ; 18(1): e13263, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34505343

RESUMEN

Food choice for children has important implications in establishing early-life dietary habits and preferences. Food choice for children has been studied as parent-child dyad dynamics, but little is known about the extended system of relationships in maternal food choice for children. The objective of this study was to understand the functions of mothers' social networks in the food choices that mothers make for their children ages 1 to 5 years old in rural Mexico. In-depth interviews were conducted with 46 participants in three rural communities. The interviews inquired about participants' child-feeding practices, personal and local beliefs about child feeding and the individuals with whom they had conversations about food and child feeding. All interviews were conducted in Spanish, audio-recorded, transcribed verbatim, verified for quality and analysed using the constant comparative method. Five interconnected networks emerged, consisting of household family, non-household family, community, children's initial school and health and nutritional programme personnel. Each network had functions in food choice that ranged from shared food decision-making in the household family network to imparting formal dietary guidance in the health and nutritional programme personnel network. Across the networks, professionals, participants' mothers and mothers-in-law, community senior women and other women with children emerged as prominent figures whom participants would turn to for child-feeding advice. These findings provide empirical evidence that social networks, as an organized system of interconnected relationships, have vital functions in establishing social norms for food choices made for children that can be leveraged to promote healthy food choices.


Asunto(s)
Conducta Alimentaria , Preferencias Alimentarias , Preescolar , Femenino , Humanos , Lactante , México , Madres , Red Social
20.
Int J Mol Sci ; 22(24)2021 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-34948050

RESUMEN

α-Synuclein (αSyn) species can be detected in synaptic boutons, where they play a crucial role in the pathogenesis of Parkinson's Disease (PD). However, the effects of intracellular αSyn species on synaptic transmission have not been thoroughly studied. Here, using patch-clamp recordings in hippocampal neurons, we report that αSyn oligomers (αSynO), intracellularly delivered through the patch electrode, produced a fast and potent effect on synaptic transmission, causing a substantial increase in the frequency, amplitude and transferred charge of spontaneous synaptic currents. We also found an increase in the frequency of miniature synaptic currents, suggesting an effect located at the presynaptic site of the synapsis. Furthermore, our in silico approximation using docking analysis and molecular dynamics simulations showed an interaction between a previously described small anti-amyloid beta (Aß) molecule, termed M30 (2-octahydroisoquinolin-2(1H)-ylethanamine), with a central hydrophobic region of αSyn. In line with this finding, our empirical data aimed to obtain oligomerization states with thioflavin T (ThT) and Western blot (WB) indicated that M30 interfered with αSyn aggregation and decreased the formation of higher-molecular-weight species. Furthermore, the effect of αSynO on synaptic physiology was also antagonized by M30, resulting in a decrease in the frequency, amplitude, and charge transferred of synaptic currents. Overall, the present results show an excitatory effect of intracellular αSyn low molecular-weight species, not previously described, that are able to affect synaptic transmission, and the potential of a small neuroactive molecule to interfere with the aggregation process and the synaptic effect of αSyn, suggesting that M30 could be a potential therapeutic strategy for synucleinopathies.


Asunto(s)
Isoquinolinas/farmacología , Neuronas/citología , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Animales , Benzotiazoles/farmacología , Células Cultivadas , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Unión Proteica , Dominios Proteicos , Ratas , Transmisión Sináptica
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