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1.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674160

RESUMO

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.


Assuntos
Potássio , Simportadores de Sódio-Bicarbonato , Animais , Camundongos , Bicarbonatos/metabolismo , Sítios de Ligação , Antiportadores de Cloreto-Bicarbonato/metabolismo , Antiportadores de Cloreto-Bicarbonato/genética , Cloretos/metabolismo , Transporte de Íons , Simulação de Dinâmica Molecular , Potássio/metabolismo , Sódio/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismo , Simportadores de Sódio-Bicarbonato/genética
2.
J Nutr ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582386

RESUMO

Although there is growing global momentum behind food systems strategies to improve planetary and human health-including nutrition-there is limited evidence of what types of food systems interventions work. Evaluating these types of interventions is challenging due to their complex and dynamic nature and lack of fit with standard evaluation methods. In this article, we draw on a portfolio of 6 evaluations of food systems interventions in Africa and South Asia that were intended to improve nutrition. We identify key methodological challenges and formulate recommendations to improve the quality of such studies. We highlight 5 challenges: a lack of evidence base to justify the intervention, the dynamic and multifaceted nature of the interventions, addressing attribution, collecting or accessing accurate and timely data, and defining and measuring appropriate outcomes. In addition to more specific guidance, we identify 6 cross-cutting recommendations, including a need to use multiple and diverse methods and flexible designs. We also note that these evaluation challenges present opportunities to develop new methods and highlight several specific needs in this space.

3.
RSC Adv ; 14(8): 5222-5233, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38344003

RESUMO

The increase in and concern about neurodegenerative diseases continue to grow in an increasingly long-lived world population. Therefore, the search for new drugs continues to be a priority for medicinal chemistry. We present here the synthesis of a series of compounds with acetamide nuclei. Their structures were established using UV-Visible, NMR, HRMS and IR techniques. Furthermore, we report the crystal structures that were obtained from compounds 5a-5d by X-ray diffraction. The compounds were evaluated as potential inhibitors of the monoxidase enzymes; A (MAO-A) and B (MAO-B), and cholinesterases; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) through in silico studies using the induced fit docking (IFD) method and binding free energy (ΔGbind) calculations by the MMGBSA method. Interestingly, compounds 5b, 5c and 5d showed much better ΔGbind than the reference drug Zonisamide. Compound 5c is the best in the series, which indicates a potential selective affinity of our compounds against MAO-B, which could be a promising finding in the search for new drugs for Parkinson's disease treatment. The acetamide crystal exhibits moderate NLO properties suggesting that it could be considered a potential candidate for application in nonlinear optical devices.

4.
Mar Pollut Bull ; 200: 116092, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38359479

RESUMO

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.


Assuntos
Tartarugas , Poluentes Químicos da Água , Animais , Microplásticos , Plásticos/química , México , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Região do Caribe , Nylons
5.
Matern Child Nutr ; 20 Suppl 3: e13616, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38204287

RESUMO

Complementary feeding practices are greatly influenced by local contexts. Therefore, national home-grown evidence, policies and guidelines are critical to improving infant and young children's diets. This Special Issue has provided a comprehensive, evidence-based analysis of the situation, gaps and context-specific opportunities for improving young children's diets in Kenya. The primary research findings of the Special Issue supported the identification of a set of recommendations articulated across the four systems (food, health, water, sanitation and hygiene [WASH] and social protection) to improve food availability and accessibility in Kenya at the national and subnational levels. It is anticipated that the decentralised government functions seen in Kenya provide a strong opportunity to develop and mainstream context-specific recommendations into action. This Special Issue recommends adopting a multi-sectoral systems approach, including a shared vision, joint planning, implementation and monitoring, towards improving young children's diets with a focus on service delivery as well as scaled-up community social behaviour change interventions. In particular, the approach should entail advocacy for policy revisions for service delivery that support complementary feeding and development of costed implementation strategies in support of the same, across four critical systems-food, health, WASH and social protection, along with, the strengthening of national coordination, monitoring and accountability structures as per the Kenya Nutrition Action Plan. Finally, the development of a legal framework for enhanced accountability from all relevant sectors towards sustainable, nutritious, safe and affordable children's diets. These recommendations provide a clear direction in addressing the complementary feeding challenges, which the primary research of this Special Issue has presented.


Assuntos
Estado Nutricional , Políticas , Pré-Escolar , Criança , Lactente , Humanos , Quênia , Alimentos , Governo
6.
Matern Child Nutr ; 20 Suppl 3: e13475, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37789710

RESUMO

The Kenyan Ministry of Health (MOH) and a consortium of nutritionists, researchers and communication, and design specialists developed a novel approach to create an evidence-based recipe book promoting complementary feeding (CF) in Kenya. The ADAPT approach includes five steps: applied research (A), dialogue with stakeholders (D), adapted behaviour change communication (BCC) theories (A), purpose-driven visual communication (P), and tailoring to priority audiences (T). Through this approach, the recipe book addresses key knowledge gaps using behaviour change theories and visual communication best practice to increase accessibility, acceptability, retention and motivation for behaviour change. The book addresses barriers to CF identified through formative applied research. Dialogue with stakeholders helped ensure cultural appropriateness and the book's alignment with MOH recommendations and key messages. The book uses behaviour change theories to approach the reader in a respectful way that motivates behaviour change. The use of consistent, purpose-driven visuals helps ensure key messages are easily understood and accessible to all caregivers regardless of literacy level. The book's tone and content are tailored to its audiences' attributes, needs and preferences. This five-step process inspired the development of ADAPT, a novel approach that integrates behaviour change and visual communication for greater impact. This paper outlines how the consortium used the ADAPT approach to develop an evidence-based book that thoughtfully and holistically addresses a wide range of barriers, provides practical solutions and increases self-efficacy around CF. It offers a blueprint for public health practitioners from any field who are interested in using visual behaviour change communication to promote healthy behaviour.


Assuntos
Educação em Saúde , Promoção da Saúde , Lactente , Humanos , Quênia , Cuidadores , Fenômenos Fisiológicos da Nutrição do Lactente
7.
Int J Mol Sci ; 24(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003447

RESUMO

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.


Assuntos
Células-Tronco Mesenquimais , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Fenótipo , Células-Tronco Mesenquimais/metabolismo
8.
Cureus ; 15(10): e46524, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37927772

RESUMO

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.

9.
Entropy (Basel) ; 25(8)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37628237

RESUMO

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%.

10.
BMC Psychol ; 11(1): 115, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37060098

RESUMO

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.


Assuntos
COVID-19 , Pandemias , Humanos , Estudos Transversais , Estudantes de Odontologia , COVID-19/epidemiologia , Aprendizagem , Universidades
11.
Int J Mol Sci ; 24(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36901904

RESUMO

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.


Assuntos
Cálcio , Canais de Cátion TRPV , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Células Epiteliais/metabolismo , Sequências Hélice-Alça-Hélice , Mamíferos/metabolismo , Canais de Cátion TRPV/metabolismo , Humanos
12.
Pathogens ; 12(2)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36839522

RESUMO

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.

13.
Matern Child Nutr ; 19(1): e13447, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36349477

RESUMO

Using a quasi-experimental design, our study aimed to determine the effectiveness of the 'Eggs Make Kids Sharp & Bright and Strong & Active' demand-creation campaign in Nigeria. The intervention arm received emotionally compelling radio and television advertisements about eggs, and was exposed to promotional activities and advertising about eggs at points of purchase, schools and health facilities; the comparison arm received no intervention. Children 6-59 months of age (intervention: n = 1359; comparison: n = 1485) were assessed 14 months apart. Intent-to-treat analyses with analysis of covariance method assessed the impact of the intervention on caregivers' behaviour towards eggs, caregivers' willingness to pay for eggs, availability of eggs in households, and consumption of eggs by children 6-59 months of age. Analyses were adjusted for possible confounders and perceived effects of COVID-19 on finances and food consumption. Compared to the comparison arm, the intervention arm showed a greater prevalence of household egg acquisition (odds ratio = 1.34, p < 0.0001), and larger improvements in caregiver self-efficacy (ß = 0.242, p = 0.004) and intent to feed eggs to children (ß = 0.080, p = 0.021). No effects were found on children's egg consumption or caregivers' reported willingness to pay for eggs. The lack of impact on child egg consumption despite increased acquisition of eggs and caregiver self-efficacy suggests that other barriers to child consumption may exist. Additional research should further investigate factors that may influence intrahousehold distribution of eggs and whether these may also influence other nutritious foods.


Assuntos
COVID-19 , Criança , Humanos , Pré-Escolar , Nigéria , Ovos , Fenômenos Fisiológicos da Nutrição Infantil , Características da Família
14.
Matern Child Nutr ; 19(1): e13442, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36353982

RESUMO

Adequate intake of high-quality nutritious foods during infancy and early childhood is critical to achieving optimal growth, cognitive and behavioural development, and economic productivity later in life. Integrating high-quality and nutrient-dense animal source foods (ASFs), a major source of protein and micronutrients, into children's diets is increasingly considered essential to reducing the global burden of malnutrition in low- and middle-income countries. While eggs are an ASF that shows promise for mitigating child undernutrition, interventions promoting egg consumption among children have had mixed results in improving egg intake and child growth outcomes. As part of an evaluation of a demand creation campaign promoting egg consumption, qualitative research was carried out in September 2019 to assess sociocultural and household factors affecting egg intake among young children living in Kaduna State, Nigeria, where a thriving egg industry and childhood stunting rates of 50% exist. Methods included freelisting exercises (11), key informant interviews (11), in-depth interviews (25) and FGDs (4). Results illuminated cultural rules that restrict egg consumption among children living in low-income households. These rules and norms reflect social and economic valuations that foster male dominance in household decision-making and guide food purchasing and intrahousehold food allocation that allow men to consume eggs more regularly. Study results highlight sociocultural considerations when selecting food interventions to address child malnutrition in low-income contexts. Interventions encouraging increased consumption of ASFs, and specifically eggs in young children, should be informed by formative research to understand sociocultural norms and beliefs guiding egg consumption.


Assuntos
Transtornos da Nutrição Infantil , Ovos , Animais , Criança , Pré-Escolar , Masculino , Humanos , Nigéria , Dieta , Abastecimento de Alimentos , Características da Família
15.
Appetite ; 180: 106370, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36375600

RESUMO

Dramatic changes in daily life are leading to increased rates of obesity and non-communicable diseases (NCD) in Kenya, including among children. Parenting plays a vital role in helping children establish healthy eating habits to prevent obesity and NCDs. The objective of this study was to describe parenting identity and how attributes of parenting influence food parenting practices in an urban Kenyan context. A qualitative study design was employed with 18 participants recruited using quota sampling to include parents who were born in (n = 8) or migrated to Nairobi in the last five years (n = 10). In-depth qualitative interviews were conducted by an experienced ethnographic interviewer that inquired about parenting identity and food parenting practices. Transcripts were analyzed using thematic coding in a multi-step and emergent process. Parents described their parenting identities as an integration of tradition and personal experiences during their upbringing with the modern realities of daily life. Their own experiences with discipline, modern urban lifestyles, and social pressures were dominant influences on their identities. Parenting identities included four distinct but related attributes: good disciplinarian, trustworthy, protective, and balanced provider and nurturer. Food parenting practices were described as expressions of parenting identity and included the goals: children becoming better eaters; nourishing through food; impart joy; and bonding. The study findings illustrate the influence of modern urban lifestyles on food parenting identities and practices. Understanding emerging identities and practices in rapidly changing low- and middle-income countries (LMIC) contexts is essential for health promoting policies and programs.


Assuntos
Nível de Saúde , Pais , Criança , Humanos , Quênia , Pesquisa Qualitativa , Obesidade
16.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1530105

RESUMO

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.


Assuntos
Humanos
18.
J Med Chem ; 65(22): 15014-15027, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36378530

RESUMO

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.


Assuntos
Neoplasias , Humanos , Relação Estrutura-Atividade , Sítios de Ligação , Proliferação de Células , Modelos Moleculares , Células MCF-7
19.
Arch Med Res ; 53(7): 673-679, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36244846

RESUMO

BACKGROUND: Activation of the renin-angiotensin-aldosterone axis with elevation of inflammatory markers and the resulting fibrosis play a very important role in atrial remodeling in patients with atrial fibrillation (AF), which is associated with post-cardioversion recurrence. AIM OF THE STUDY: The purpose of the study was to describe the time course of angiotensin II (AngII), aldosterone, and of the amino terminal pro-peptide of type III pro-collagen (PIIINP) following cardioversion, and their association with arrhythmia recurrence. METHODS: Ninety-nine subjects with long-standing, persistent, non-valvular atrial fibrillation who underwent successful electrical cardioversion were included, with a 6 month follow up. Angiotensin II (AngII), aldosterone and PIIINP concentrations were measured at 0, 1, 7, 30, and 180 d. Two groups were formed for the analysis: continuing sinus rhythm and recurrence of AF. RESULTS: 53% of the subjects experienced recurrence of AF. Subjects with recurrence had larger left atrial diameters and lower global peak atrial longitudinal strain (8.7 vs. 19.7%; p <0.001), higher levels of AngII (431.85 vs. 257.97 pg/mL; p = 0.003) at 180 d, higher pre-cardioversion levels of aldosterone, (11.42 vs. 5.46 pg/mL; p = 0.048) at 1 d (12.01 vs. 5.05 pg/mL; p = 0.004) and at 180 d (12.66 vs. 7.51 pg/mL; p = 0.011). There were no differences in PIIINP levels between both groups. CONCLUSIONS: Electrical post-cardioversion recurrence in subjects with long-standing, persistent AF is associated with elevated levels of AngII and aldosterone.


Assuntos
Fibrilação Atrial , Remodelamento Atrial , Humanos , Cardioversão Elétrica/métodos , Fibrilação Atrial/terapia , Aldosterona , Angiotensina II , Resultado do Tratamento , Biomarcadores , Recidiva
20.
Pathogens ; 11(10)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36297267

RESUMO

Since the first report on isolation of porcine adenovirus serotype 5 (PAdV-5, species Porcine mastadenovirus C (PAdV-C)) from pigs with respiratory illness in Japan in 1987, PAdV-5 have been detected in a few fecal samples from healthy pigs and in some environmental samples. To date, only a single PAdV-5 strain (isolate HNF-70 from 1987) has been analyzed for the complete genome. We report here high detection rates of PAdV-5 (25.74%, 26/101 fecal samples) in diarrheic pigs at 3 different farms in the Caribbean country of Dominican Republic. After a long gap, the complete deduced amino acid sequences of the DNA-dependent DNA polymerase (pol) and hexon of two PAdV-5 strains (GES7 and Z11) were determined, revealing >99% sequence identities between PAdV-5 strains (HNF-70, GES7 and Z11) detected in different parts of the world and during different time periods (1987, and 2020−2021). By phylogenetic analysis, the putative hexon and pol of HNF-70, GES7 and Z11 exhibited similar clustering patterns, with the PAdV-5 strains forming a tight cluster near ruminant AdVs, distinct from the species PAdV-A and -B. GES7 and Z11 retained the various conserved features present in the putative pol and major late promoter region of HNF-70. Considering the paucity of data on current epidemiological status and genetic diversity of PAdV in porcine populations, our findings warrant similar studies on PAdV-5 and other PAdVs in clinically ill and healthy pigs. To our knowledge, this is the first report on detection and molecular characterization of PAdV-5 (PAdV-C) from diarrheic pigs.

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