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1.
Biochem Biophys Rep ; 38: 101716, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38737726

RESUMO

The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis. Six SNPs were determined through genotyping. T2D patients (n = 29) and healthy subjects (n = 25) with a median age of 57 and 50, respectively, were recruited. An increased enzyme expression and a diminished NAT2 enzymatic activity were found in cells of T2D patients compared to the control group, while NAT1 was negatively correlated with body fat percentage and BMI. In contrast, Sirtuin inhibition increased NAT2 activity, while Sirtuin agonism decreased its activity in both groups. The analysis of NAT2 SNPs showed a higher frequency of rapid acetylation haplotypes in T2D patients compared to the control group, possibly associated as a risk factor for diabetes. The enzymatic expression of CD3+NAT2+ cells was higher in the rapid acetylators group compared to the slow acetylators group. The levels and activity of NAT1 were associated with total cholesterol and triglycerides. Meanwhile, CD3+NAT2+ cells and NAT2 activity levels were associated with HbA1c and glucose levels. The results indicate that NAT2 could be involved in metabolic processes related to the development of T2D, due to its association with glucose levels, HbA1c, and the altered SIRT-NAT axis. NAT1 may be involved with dyslipidaemias in people who are overweight or obese.

2.
Gac Med Mex ; 160(1): 1-8, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753562

RESUMO

BACKGROUND: Protein interactions participate in many molecular mechanisms involved in cellular processes. The human TATA box binding protein (hTBP) interacts with Antennapedia (Antp) through its N-terminal region, specifically via its glutamine homopeptides. This PolyQ region acts as a binding site for other transcription factors under normal conditions, but when it expands, it generates spinocerebellar ataxia 17 (SCA17), whose protein aggregates in the brain prevent its correct functioning. OBJECTIVE: To determine whether the hTBP glutamine-rich region is involved in its interaction with homeoproteins and the role it plays in the formation of protein aggregates in SCA17. MATERIAL AND METHODS: We characterized hTBP interaction with other homeoproteins using BiFC, and modeled SCA17 in Drosophila melanogaster by targeting hTBPQ80 to the fly brain using UAS/GAL4. RESULTS: There was hTBP interaction with homeoproteins through its glutamine-rich region, and hTBP protein aggregates with expanded glutamines were found to affect the locomotor capacity of flies. CONCLUSIONS: The study of hTBP interactions opens the possibility for the search for new therapeutic strategies in neurodegenerative pathologies such as SCA17.


ANTECEDENTES: Las interacciones proteicas participan en una gran cantidad de mecanismos moleculares que rigen los procesos celulares. La proteína de unión a la caja TATA humana (hTBP) interacciona con Antennapedia (Antp) a través de su extremo N-terminal, específicamente a través de sus homopéptidos de glutaminas. Esta región PolyQ sirve como sitio de unión a factores de transcripción en condiciones normales, pero cuando se expande genera la ataxia espinal cerebelosa 17 (SCA17), cuyos agregados proteicos en el cerebro impiden su funcionamiento correcto. OBJETIVO: Determinar si la región rica en glutaminas de hTBP interviene en su interacción con homeoproteínas y el papel que tiene en la formación de agregados proteicos en SCA17. MATERIAL Y MÉTODOS: Se caracterizó la interacción de hTBP con otras homeoproteínas usando BiFC y se modeló SCA17 en Drosophila melanogaster dirigiendo hTBPQ80 al cerebro de las moscas usando UAS/GAL4. RESULTADOS: Existió interacción de hTBP con homeoproteínas a través de su región rica en glutaminas. Los agregados proteicos de hTBP con las glutaminas expandidas afectaron la capacidad locomotriz de las moscas. CONCLUSIONES: El estudio de las interacciones de hTBP abre la posibilidad para la búsqueda de nuevas estrategias terapéuticas en patologías neurodegenerativas como SCA17.


Assuntos
Modelos Animais de Doenças , Drosophila melanogaster , Ataxias Espinocerebelares , Proteína de Ligação a TATA-Box , Animais , Drosophila melanogaster/metabolismo , Ataxias Espinocerebelares/metabolismo , Ataxias Espinocerebelares/genética , Proteína de Ligação a TATA-Box/metabolismo , Proteína de Ligação a TATA-Box/genética , Humanos , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Glutamina/metabolismo , Agregados Proteicos/fisiologia , Peptídeos/metabolismo , Encéfalo/metabolismo
3.
J Biol Chem ; : 107373, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38762183

RESUMO

Motile cilia on the cell surface produce fluid flows in the body and abnormalities in motile cilia cause primary ciliary dyskinesia (PCD). Dynein axonemal assembly factors 6 (DNAAF6), a causative gene of PCD, was isolated as an interacting protein with La ribonucleoprotein 6 (LARP6) that regulates ciliogenesis in multi-ciliated cells (MCCs). In MCCs of Xenopus embryos, LARP6 and DNAAF6 were co-localized in biomolecular condensates termed dynein axonemal particles (DynAPs) and synergized to control ciliogenesis. Moreover, Tubulin alpha 1c like (TUBA1CL) mRNA encoding α-Tubulin protein that is a major component of ciliary axoneme was identified as a target mRNA regulated by binding LARP6. While DNAAF6 was necessary for high α-Tubulin protein expression near the apical side of Xenopus MCCs during ciliogenesis, its mutant, which abolishes binding with LARP6, was unable to restore the expression of α-Tubulin protein near the apical side of MCCs in Xenopus DNAAF6 morphant. These results indicated that the binding of LARP6 and DNAAF6 in DynAPs regulates highly expressed α-Tubulin protein near the apical side of Xenopus MCCs during ciliogenesis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38666438

RESUMO

Introduction: Metabolic syndrome (MetS) is a pathophysiological condition defined by a set of metabolic alterations such as hypertriglyceridemia, hyperglycemia, hypertension, low HDL-c levels, and visceral obesity. Its presence identifies people with an increased risk of developing cardiovascular diseases and type 2 diabetes; however, the lack of practical and reliable methods for its diagnosis limits the identification of people with this condition. In this sense, the objective of this study was to analyze the diagnostic utility of markers derived from the lipid profile [triglyceride-glucose (TyG) index and the ratios total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-c), triglyceride (TG)/HDL-c, low-density lipoprotein cholesterol/HDL-c, fasting blood glucose (FBG)/HDL-c, and white blood cell/HDL-c] in the determination of MetS. Methods: A retrospective study was designed that included 619 individuals. A logistic regression model was used to evaluate the associations of the different markers with MetS, and the cutoff points of the markers were determined through an analysis of receiver operating characteristic curves and the Youden Index. Results: A positive and significant association was observed between all markers and the presence of MetS. The cutoff values for the markers that best predicted MetS were TyG ≥ 4.8 (sensitivity = 91.4%, specificity = 74.3%), TC/HDL-c ≥ 3.7 (sensitivity = 74.3%, specificity = 75.7%), TG/HDL-c ≥ 3.3 (sensitivity = 82.5%, specificity = 84.0%), and FBG/HDL-c ≥ 2.0 (sensitivity = 85.1%, specificity = 79.7%). Conclusion: Our study demonstrated the diagnostic relevance of the different markers in detecting MetS, suggesting that these ratios may be useful in clinical practice for the opportune and accurate diagnosis of MetS.

5.
PLoS One ; 19(4): e0300420, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662716

RESUMO

Discrepancies between the measurement of body mass index (BMI) and metabolic health status have been described for the onset of metabolic diseases. Studying novel biomarkers, some of which are associated with metabolic syndrome, can help us to understand the differences between metabolic health (MetH) and BMI. A group of 1469 young adults with pre-specified anthropometric and blood biochemical parameters were selected. Of these, 80 subjects were included in the downstream analysis that considered their BMI and MetH parameters for selection as follows: norm weight metabolically healthy (MHNW) or metabolically unhealthy (MUNW); overweight/obese metabolically healthy (MHOW) or metabolically unhealthy (MUOW). Our results showed for the first time the differences when the MetH status and the BMI are considered as global MetH statures. First, all the evaluated miRNAs presented a higher expression in the metabolically unhealthy group than the metabolically healthy group. The higher levels of leptin, IL-1b, IL-8, IL-17A, miR-221, miR-21, and miR-29 are directly associated with metabolic unhealthy and OW/OB phenotypes (MUOW group). In contrast, high levels of miR34 were detected only in the MUNW group. We found differences in the SIRT1-PGC1α pathway with increased levels of SIRT1+ cells and diminished mRNA levels of PGCa in the metabolically unhealthy compared to metabolically healthy subjects. Our results demonstrate that even when metabolic diseases are not apparent in young adult populations, MetH and BMI have a distinguishable phenotype print that signals the potential to develop major metabolic diseases.


Assuntos
Índice de Massa Corporal , MicroRNAs , Feminino , Humanos , Masculino , Adulto Jovem , Biomarcadores/sangue , Leptina/sangue , Leptina/genética , Leptina/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , MicroRNAs/genética , MicroRNAs/sangue , MicroRNAs/metabolismo , Obesidade/genética , Obesidade/metabolismo , Fenótipo , Sirtuína 1/genética , Sirtuína 1/metabolismo
6.
PLoS One ; 19(2): e0299543, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422035

RESUMO

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.


Assuntos
Resistência à Insulina , Adulto Jovem , Humanos , Adolescente , Adulto , Resistência à Insulina/genética , Estudos Transversais , Estratificação de Risco Genético , Alanina , Arginina
7.
PLoS One ; 19(1): e0294494, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38170702

RESUMO

Establishing the infant's gut microbiota has long-term implications on health and immunity. Breastfeeding is recognized as the best practice of infant nutrition in comparison with formula feeding. We evaluated the effects of the primary feeding practices by analyzing the infant growth and the potential association with gut diseases. A cross-sectional and observational study was designed. This study included 55 mothers with infants, who were divided according to their feeding practices in breastfeeding (BF), formula feeding (FF), and combined breast and formula feeding (CF). Anthropometric measurements of the participants were recorded. Additionally, non-invasive fecal samples from the infants were collected to analyze the microbiota by sequencing, immunoglobulin A (IgA) concentration (ELISA), and volatile organic compounds (gas chromatography with an electronic nose). Results showed that the microbiota diversity in the BF group was the highest compared to the other two groups. The IgA levels in the BF group were twice as high as those in the FF group. Moreover, the child´s growth in the BF group showed the best infant development when the data were compared at birth to the recollection time, as noted by the correlation with a decreased concentration of toxic volatile organic compounds. Interestingly, the CF group showed a significant difference in health status when the data were compared with the FF group. We conclude that early health practices influence children's growth, which is relevant to further research about how those infants' health evolved.


Assuntos
Microbioma Gastrointestinal , Compostos Orgânicos Voláteis , Recém-Nascido , Lactente , Feminino , Criança , Humanos , Estudos Transversais , Aleitamento Materno , Imunoglobulina A , Fórmulas Infantis
8.
Vet Med Sci ; 10(1): e1317, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37902142

RESUMO

BACKGROUND: Congenital entropion is the most frequent ocular disorder in newborn lambs of certain sheep breeds, which, if not treated, can result in complete blindness and death due to starvation. OBJECTIVES: The aims of this study were to compare the spontaneous healing of entropion in two breeds and assess the outcome of cases with and without therapeutic intervention. METHODS: A total of 158 entropion cases (119 Ile de France and 39 Romane) were investigated, and swab samples were collected from the cornea and conjunctiva of 73 of the affected lambs for bacteriological investigation. In addition, an ocular intervention was carried out in 123 affected animals. RESULTS: The Romane breed developed entropion at an average age of 7 days compared to the Ile de France, which developed it at an average age of 1 day. Likewise, significant differences were found between bilateral and unilateral involvement in both breeds. Meanwhile, 22.1% of cases recovered spontaneously, and the highest rate of spontaneous recovery without intervention was observed in the Romane breed (66%). Bacteria isolated from ocular samples included Staphylococcus spp. (42.5%), Bacillus spp. (21.9%), Trueperella pyogenes (13.7%), Corynebacterium spp. (12.3%) and Escherichia coli (9.6%). CONCLUSIONS: The results of the study showed that the onset time of entropion, bilateral involvement, the severity of the process and the need for re-treatment were higher in the Ile de France breed than in the Romane breed. Likewise, the Romane breed showed a higher degree of spontaneous recovery of entropion.


Assuntos
Entrópio , Doenças dos Ovinos , Ovinos , Animais , Entrópio/cirurgia , Entrópio/veterinária , Carneiro Doméstico , França/epidemiologia
9.
Dev Psychol ; 60(2): 211-227, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37843515

RESUMO

Culture is a key determinant of children's development both in its own right and as a measure of generalizability of developmental phenomena. Studying the role of culture in development requires information about participants' demographic backgrounds. However, both reporting and treatment of demographic data are limited and inconsistent in child development research. A barrier to reporting demographic data in a consistent fashion is that no standardized tool currently exists to collect these data. Variation in cultural expectations, family structures, and life circumstances across communities make the creation of a unifying instrument challenging. Here, we present a framework to standardize demographic reporting for early child development (birth to 3 years of age), focusing on six core sociodemographic construct categories: biological information, gestational status, health status, community of descent, caregiving environment, and socioeconomic status. For each category, we discuss potential constructs and measurement items and provide guidance for their use and adaptation to diverse contexts. These items are stored in an open repository of context-adapted questionnaires that provide a consistent approach to obtaining and reporting demographic information so that these data can be archived and shared in a more standardized format. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Desenvolvimento Infantil , Classe Social , Criança , Humanos , Pré-Escolar , Inquéritos e Questionários , Nível de Saúde
10.
Genesis ; 62(1): e23561, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37830148

RESUMO

Hox genes encode transcription factors that play an important role in establishing the basic body plan of animals. In Drosophila, Antennapedia is one of the five genes that make up the Antennapedia complex (ANT-C). Antennapedia determines the identity of the second thoracic segment, known as the mesothorax. Misexpression of Antennapedia at different developmental stages changes the identity of the mesothorax, including the muscles, nervous system, and cuticle. In Drosophila, Antennapedia has two distinct promoters highly regulated throughout development by several transcription factors. Antennapedia proteins are found with other transcription factors in different ANTENNAPEDIA transcriptional complexes to regulate multiple subsets of target genes. In this review, we describe the different mechanisms that regulate the expression and function of Antennapedia and the role of this Hox gene in the development of Drosophila.


Assuntos
Proteínas de Drosophila , Fatores de Transcrição , Animais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética
12.
J Nutr ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37918674

RESUMO

BACKGROUND: Vitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality. OBJECTIVES: The study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency. METHODS: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 µg (2-3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices. RESULTS: LTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups. CONCLUSIONS: Providing daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842.

13.
Biochem Biophys Rep ; 36: 101558, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37881409

RESUMO

The monocytes are key components of innate immunity, as they can differentiate into phagocytic cells or macrophages with proinflammatory or anti-inflammatory phenotypes. The gamma-aminobutyric acid (GABA) and adenosine triphosphate (ATP), two known neurotransmitters, are two environmental signals that contribute to the differentiation of monocytes into macrophages and their subsequent polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. Although monocytes and macrophages express proteins related to GABA and ATP-mediated response (GABAergic and purinergic systems, respectively), it is unknown whether changes in their expression occur during monocyte activation or their differentiation and polarization into macrophages. Therefore, we evaluated the expression levels of GABAergic and purinergic signaling components in the THP-1 monocyte cell line and their changes during monocyte activation, differentiation, and polarization to M1 proinflammatory macrophages. Our results showed that activated monocytes are characterized by increased expression of two GABAergic components, the GABA transporter 2 (GAT-2) and the glutamic acid decarboxylase (GAD)-67, an enzyme involved in GABA synthesis. Also, monocytes showed a pronounced expression of the purinergic receptors P2X4 and P2X7. Interestingly, during differentiation, monocytes increased the expression of the ß2 subunit of GABA A-type receptor (GABA-AR), while the purinergic receptors P2X1 and P2X1del were reduced. In contrast, proinflammatory M1 macrophages showed a reduced expression in the α4 subunit of GABA-AR and GAD67, while P2X4 and P2X7 were overexpressed. These results indicate that dynamical changes in the GABAergic and purinergic components occur during the transition from monocytes to macrophages. Since GABA and ATP are two neurotransmitters, our results suggest that monocytes and macrophages respond to neurotransmitter-induced stimulation and may represent a path of interaction between the nervous and immune systems during peripheral inflammation and neuroinflammation development.

14.
Clin Nucl Med ; 48(12): e574, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796188

RESUMO

ABSTRACT: A 29-year-old man diagnosed with monkeypox infection underwent an 18 F-FDG PET/CT for the study of organic involvement in the context of a nonsatisfactory clinical evolution. He had a history of HIV (with undetectable viral load). FDG PET/CT showed multiple hypermetabolic lymphadenopathies and bilateral pulmonary nodules with mild 18 F-FDG uptake.


Assuntos
Infecções por HIV , Mpox , Masculino , Humanos , Adulto , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos
15.
Sci Rep ; 13(1): 15162, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704704

RESUMO

wingless expression is exquisitely regulated by different factors and enhancers in the imaginal wing discs of Drosophila melanogaster in four domains: the dorsal band, the dorso-ventral boundary, and the inner and outer ring domains. tonalli is a trithorax group gene that encodes a putative SUMO E3 ligase that binds to chromatin to regulate the expression of its targets, including the Hox genes. However, its role in modulating gene expression is barely known. Here, we show that TnaA modulates the wingless expression at two domains of the wing disc, the dorso-ventral boundary and the inner ring. At first, tonalli interacts genetically with Notch to form the wing margin. In the inner ring domain, TnaA modulates wingless transcription. When the dosage of TnaA increases in or near the inner ring since early larval stages, this domain expands with a rapid increase in wingless expression. TnaA occupies the wingless Inner Ring Enhancer at the wing disc, meanwhile it does not affect wingless expression directed by the Ventral Disc Enhancer in leg discs, suggesting that TnaA acts as a wingless enhancer-specific factor. We describe for the first time the presence of TnaA at the Inner Ring Enhancer as a specific regulator of wingless in the development of wing boundaries.


Assuntos
Drosophila melanogaster , Drosophila , Animais , Drosophila melanogaster/genética , Discos Imaginais , Larva , Ubiquitina-Proteína Ligases
16.
Nutr Hosp ; 40(5): 960-966, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37732356

RESUMO

Introduction: Introduction: advanced glycation end-products (AGEs) interact with the receptor for AGEs (RAGE). Full-length RAGE is associated with intracellular signal transduction, and soluble-RAGE (sRAGE) lacks the transmembrane and cytoplasmic domains, acting as a competitive inhibitor of AGEs-RAGE binding. sRAGE levels in healthy children are associated with cell surface expression of RAGE. However, the expression of RAGE has not been explored in childhood obesity. Objective: the study aim was to evaluate the sRAGE levels and the gene expression of RAGE in children and its association with cardiometabolic markers. Methods: this is a cross-sectional study with 6-11-year children, 20 with overweight and 20 with obesity. Anthropometric measurements included waist circumference (cm) (WC), neck circumference (NC), weight (kg), fat mass (%), trunk fat (kg), muscular mass (kg), height (cm), and body mass index (BMI) (kg/m2). Blood samples following an overnight fast were collected to measure glucose (mg/dl) and lipid profile with colorimetric methods. sRAGE was determined in serum using the enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription (RT-qPCR) was performed to analyze RAGE transcripts in peripheral blood mononuclear cells isolated by Ficoll®-Hypaque. Results: we found higher RAGE (p = 0.0315) and lower sRAGE (p = 0.0305) levels in the obesity group. sRAGE level showed a negative correlation with RAGE (r = -0.35) and BMI (r = -0.24), and positive with HDL-cholesterol (r = 0.29). Regression analysis suggests that HDL-C and RAGE levels are predictors of sRAGE levels. Conclusions: expression of RAGE is associated with lower sRAGE levels in childhood obesity. Moreover, obese children show higher cardiometabolic risk markers, and a positively associated with sRAGE.


Introducción: Introducción: los productos finales de glicación avanzada (AGE) interactúan con el receptor de AGE (RAGE). El RAGE de longitud completa está asociado con la transducción de señales intracelulares y el RAGE soluble (sRAGE) carece de los dominios transmembrana y citoplásmico, actuando como un inhibidor competitivo de la unión de AGE-RAGE. Los niveles de sRAGE en niños sanos están asociados con la expresión de RAGE en la superficie celular. Sin embargo, la expresión de RAGE no se ha explorado en la obesidad infantil. Objetivo: el objetivo del estudio fue evaluar los niveles de sRAGE y la expresión génica de RAGE en niños y su asociación con marcadores cardiometabólicos. Métodos: se trata de un estudio transversal con niños de seis a once años, 20 con sobrepeso y 20 con obesidad. Las medidas antropométricas incluyeron la circunferencia de la cintura (cm) (CC), la circunferencia del cuello (NC), el peso (kg), la masa grasa (%), la grasa del tronco (kg), la masa muscular (kg), la altura (cm) y el índice de masa corporal (IMC) (kg/m2). Se tomaron muestras de sangre después de una noche de ayuno para medir glucosa (mg/dl) y el perfil de lípidos con métodos colorimétricos. Los sRAGE se determinaron en suero utilizando un ensayo inmunoabsorbente ligado a enzimas (ELISA). Se realizó una transcripción inversa cuantitativa (RT-qPCR) para analizar los transcritos de RAGE en células mononucleares de sangre periférica aisladas por Ficoll®-Hypaque. Resultados: encontramos niveles más altos de RAGE (p = 0,0315) y más bajos de sRAGE (p = 0,0305) en el grupo de obesidad. El nivel de sRAGE mostró una correlación negativa con RAGE (r = -0,35) e IMC (r = -0,24), y positiva con el colesterol HDL (r = 0,29). El análisis de regresión sugiere que los niveles de HDL-C y RAGE predicen los niveles de sRAGE. Conclusiones: la expresión de RAGE se asocia con niveles más bajos de sRAGE en la obesidad infantil. Además, los niños obesos muestran marcadores de riesgo cardiometabólico más elevados y una asociación positiva con sRAGE.

18.
Molecules ; 28(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37630269

RESUMO

Structure-activity relationship (SAR) studies allow the evaluation of the relationship between structural chemical changes and biological activity. Fluoroquinolones have chemical characteristics that allow their structure to be modified and new analogs with different therapeutic properties to be generated. The objective of this research is to identify and select the C-7 heterocycle fluoroquinolone analog (FQH 1-5) with antibacterial activity similar to the reference fluoroquinolone through in vitro, in silico, and in vivo evaluations. First, SAR analysis was conducted on the FQH 1-5, using an in vitro antimicrobial sensibility model in order to select the best compound. Then, an in silico model mechanism of action analysis was carried out by molecular docking. The non-bacterial cell cytotoxicity was evaluated, and finally, the antimicrobial potential was determined by an in vivo model of topical infection in mice. The results showed antimicrobial differences between the FQH 1-5 and Gram-positive and Gram-negative bacteria, identifying the 7-benzimidazol-1-yl-fluoroquinolone (FQH-2) as the most active against S. aureus. Suggesting the same mechanism of action as the other fluoroquinolones; no cytotoxic effects on non-bacterial cells were found. FQH-2 was demonstrated to decrease the amount of bacteria in infected wound tissue.


Assuntos
Antibacterianos , Anti-Infecciosos , Animais , Camundongos , Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Simulação de Acoplamento Molecular , Staphylococcus aureus , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Relação Estrutura-Atividade
19.
Bol Med Hosp Infant Mex ; 80(3): 177-182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37467436

RESUMO

BACKGROUND: Intravascular venous (VUC) or arterial (AUC) umbilical catheter placement is the most frequent invasive procedure in the neonatal intensive care unit (NICU). Either Wright's or Shukla's formula is used to introduce the catheters. However, Shukla's formula is associated with incorrect insertion, especially for newborns < 1500 g. This study aimed to determine by chest X-ray if Wright's formula is better than Shukla's formula for the correct placement of umbilical catheters in newborns ≤ 1500 g. METHODS: We included patients admitted to the NICU of a secondary-level hospital between 2021-2022 who received VUC or AUC through the Wright or Shukla formulas. RESULTS: A total of 129 newborns were included: 78 with VUC and 51 with AUC. In VUC, 50% with Wright and 36.8% with Shukla formulas had the correct location, (p = 0.24). In AUC, 56.6 % with Wright and 52.4% with Shukla formulas were placed correctly placed, (p = 0.76). VUC with weight < 1000 g were correctly placed in 36.4% with Wright and 33.3% with Shukla formulas (p = 0.58). VUC in newborns > 1000 g were correctly placed in 66.6% with Wright and 38.4% with Shukla formulas (p = 0.065). AUC in newborns < 1000 g were correctly placed in 45% using Wright and 42.9% Shukla formulas (p = 0.63). AUC in newborns > 1000 g were correctly placed in 80% using Wright and 57.1% Shukla formulas (p = 0.23). CONCLUSIONS: We found 13% more correctly placed VUC using Wright's formula. Moreover, Wright's formula was 29% above Shukla's VUC placement in neonates > 1000 g, although there was no significant difference due to the sample size.


INTRODUCCIÓN: La colocación de catéteres intravasculares venosos umbilicales (CVU) y arteriales (CAU) es el procedimiento invasivo más frecuente en la unidad de cuidados intensivos neonatales (UCIN). Para introducirlos se utilizan las fórmulas de Wright y de Shukla, aunque esta última podría estar asociada con una inserción incorrecta, especialmente en neonatos < 1500 g. El objetivo de este estudio fue determinar mediante radiografía de tórax cuál fórmula es mejor para la correcta colocación de catéteres umbilicales en recién nacidos ≤ 1500 g. MÉTODOS: Se incluyeron los pacientes ingresados en la UCIN de un hospital de segundo nivel entre 2021-2022 que recibieron CVU o CAU mediante las fórmulas de Wrigth o Shukla. RESULTADOS: Se incluyeron en total 129 recién nacidos: 78 CVU y 51 CAU. En CVU, Wright 50% y Shukla 36.8% tuvieron localización correcta, p = 0.24. En las CAU, Wright 56.6% y Shukla 52.4% tenían una ubicación correcta, p = 0.76. En CVU con peso < 1000 g, Wright 36.4% y Shukla 33.3% bien situados, p = 0.58. En CVU > 1000 g, Wright 66.6% y Shukla 38.4% bien situados, p = 0.065. En CAU < 1000 g, Wright 45% y Shukla 42.9%, p = 0.63. En CAU con peso > 1000 g, Wright 80% y Shukla 57.1%, p = 0.23. CONCLUSIONES: La colocación del CVU fue 13% mejor con la fórmula de Wright. La fórmula de Wright superó en el 29% la colocación del CVU en los neonatos > 1000 g en comparación con la de Shukla, aunque no hubo diferencia significativa debido al tamaño de la muestra.


Assuntos
Artérias , Unidades de Terapia Intensiva Neonatal , Humanos , Recém-Nascido , Catéteres
20.
Animals (Basel) ; 13(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37443937

RESUMO

Despite a high species diversity, skates (Rajiformes) exhibit remarkably conservative morphology and ecology. Limited trait variations occur within and between species, and cryptic species have been reported among sister and non-sister taxa, suggesting that species complexes may be subject to stabilising selection. Three sibling species are currently recognised in the Raja miraletus complex: (i) R. miraletus occurring along the Portuguese and Mediterranean coasts, (ii) R. parva in the Central-Eastern Atlantic off West Africa and (iii) R. ocellifera in the Western Indian Ocean off South Africa. In the present study, the genetic variation at mitochondrial and nuclear markers was estimated in the species complex by analysing 323 individuals sampled across most of its geographical distribution area to test the hypothesis that restricted gene flow and genetic divergence within species reflect known climate and bio-oceanographic discontinuities. Our results support previous morphological studies and confirm the known taxonomic boundaries of the three recognised species. In addition, we identified multiple weakly differentiated clades in the Northeastern Atlantic Ocean and Mediterranean, at least two additional cryptic taxa off Senegal and Angola, a pronounced differentiation of ancient South African clades. The hidden genetic structure presented here may represent a valuable support to species' conservation action plans.

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