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This study assessed the in vitro anthelmintic activity of ethyl acetate extract (Cn-EtOAc) and its bioactive fractions (CnR3 and CnR5) obtained from Chamaecrista nictitans aerial parts against two Haemonchus contortus (Hc) isolates, one resistant (strain HcIVM-R) and another susceptible (strain HcIVM-S) to ivermectin. Ferulic acid and p-coumaric acid were identified in the bioactive fractions; therefore, their commercial standards were also assessed. A colocalization analysis between the ferulic acid commercial standard and eggs of the HcIVM-R strain was performed using confocal laser scanning microscopy and the ImageJ program. The ovicidal effects of the Cn-EtOAc extract, bioactive fractions and commercial compounds were tested through the egg hatching inhibition (EHI) assay on H. contortus isolates HcIVM-R and HcIVM-S. The Cn-EtOAc caused 88â¯% and 92â¯% EHI at 5000⯵g/mL on HcIVM-R and HcIVM-S, respectively. Fractions CnR3 and CnR5 displayed the highest ovicidal activity against HcIVM-S, with effective concentrations (EC90) of 2134 and 601⯵g/mL, respectively. Meanwhile, the commercial standards ferulic acid and p-coumaric acid also resulted in higher effectiveness on the same strain, with EC90 of 57.5 and 51.1⯵g/mL. A colocalization analysis of ferulic acid and eggs of HcIVM-R revealed that this compound is localized to the cuticle surface of the embryo inside the egg parasite. The results demonstrated that both ferulic and p-coumaric acids interrupt the egg-hatching processes of the two Hc isolates. Both phenolic acids isolated from C. nictitans and commercial standards exhibited the best anthelmintic effect on HcIVM-S. These findings indicate that the phenolic acids were less effective in egg hatch inhibiting on the HcIVM-R strain compared to the HcIVM-S strain.
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Anti-Helmínticos , Ácidos Cumáricos , Haemonchus , Extratos Vegetais , Animais , Haemonchus/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Óvulo/efeitos dos fármacosRESUMO
Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon-intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients.
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Hipotireoidismo Congênito , Iodeto Peroxidase , Proteínas de Ligação ao Ferro , Mutação , Humanos , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/sangue , Chile , Iodeto Peroxidase/genética , Feminino , Masculino , Proteínas de Ligação ao Ferro/genética , Autoantígenos/genética , Lactente , Criança , Adolescente , Pré-Escolar , Recém-Nascido , Disgenesia da Tireoide/genética , Disgenesia da Tireoide/complicações , Disgenesia da Tireoide/sangueRESUMO
The study evaluated the effects of Arthrospira maxima phycobiliproteins (PBPs), rosiglitazone (RSG), and 17ß-estradiol (E) on the differentiation process of 3T3-L1 cells and on their regulation of lipogenic and inflammatory gene expression at different stages of the process. The results showed that phycobiliproteins promoted cell proliferation after 24 h of treatment. Furthermore, for all three treatments, the regulation of the highest number of markers occurred on days 6 and 12 of differentiation, regardless of when the treatment was applied. Phycobiliproteins reduced lipid droplet accumulation on days 3, 6, 10, and 13 of the adipogenic process, while rosiglitazone showed no differences compared to the control. On day 6, both phycobiliproteins and rosiglitazone positively regulated Acc1 mRNA. Meanwhile, all three treatments negatively regulated Pparγ and C/ebpα. Phycobiliproteins and estradiol also negatively regulated Ucp1 and Glut4 mRNAs. Rosiglitazone and estradiol, on the other hand, negatively regulated Ppara and Il-6 mRNAs. By day 12, phycobiliproteins and rosiglitazone upregulated Pparγ mRNA and negatively regulated Tnfα and Il-1ß. Additionally, phycobiliproteins and estradiol positively regulated Il-6 and negatively regulated Ppara, Ucp2, Acc1, and Glut4. Rosiglitazone and estradiol upregulate C/ebpα and Ucp1 mRNAs. The regulation exerted by phycobiliproteins on the mRNA expression of the studied markers was dependent on the phase of cell differentiation. The results of this study highlight that phycobiliproteins have an anti-adipogenic and anti-inflammatory effect by reducing the expression of adipogenic, lipogenic, and inflammatory genes in 3T3-L1 cells at different stages of the differentiation process.
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Células 3T3-L1 , Adipócitos , Adipogenia , Diferenciação Celular , Estradiol , Ficobiliproteínas , Rosiglitazona , Animais , Camundongos , Estradiol/farmacologia , Rosiglitazona/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/citologia , Diferenciação Celular/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Ficobiliproteínas/farmacologia , Ficobiliproteínas/metabolismo , Ficobiliproteínas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , PPAR gama/metabolismo , PPAR gama/genética , Proliferação de Células/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/genética , SpirulinaRESUMO
Sleep is a physiological process that preserves the integrity of the neuro-immune-endocrine network to maintain homeostasis. Sleep regulates the production and secretion of hormones, neurotransmitters, cytokines and other inflammatory mediators, both at the central nervous system (CNS) and at the periphery. Sleep promotes the removal of potentially toxic metabolites out of the brain through specialized systems such as the glymphatic system, as well as the expression of specific transporters in the blood-brain barrier. The blood-brain barrier maintains CNS homeostasis by selectively transporting metabolic substrates and nutrients into the brain, by regulating the efflux of metabolic waste products, and maintaining bidirectional communication between the periphery and the CNS. All those processes are disrupted during sleep loss. Brain endothelial cells express the blood-brain barrier phenotype, which arises after cell-to-cell interactions with mural cells, like pericytes, and after the release of soluble factors by astroglial endfeet. Astroglia, pericytes and brain endothelial cells respond differently to sleep loss; evidence has shown that sleep loss induces a chronic low-grade inflammatory state at the CNS, which is associated with blood-brain barrier dysfunction. In animal models, blood-brain barrier dysfunction is characterized by increased blood-brain barrier permeability, decreased tight junction protein expression and pericyte detachment from the capillary wall. Blood-brain barrier dysfunction may promote defects in brain clearance of potentially neurotoxic metabolites and byproducts of neural physiology, which may eventually contribute to neurodegenerative diseases. This chapter aims to describe the cellular and molecular mechanisms by which sleep loss modifies the function of the blood-brain barrier.
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Barreira Hematoencefálica , Privação do Sono , Barreira Hematoencefálica/metabolismo , Humanos , Animais , Privação do Sono/metabolismo , Privação do Sono/fisiopatologia , Células Endoteliais/metabolismoRESUMO
The research aimed to assess the effects of incorporating germinated Lupinus angustifolius flour into corn extrudates for different periods (3, 5, and 7 days), focusing on starch digestibility, morphological structure, thermal, and pasting properties. Extrudate with germinated lupinus flour for 7 days (EG7) significantly increased the content of slowly digestible starch up to 10.56% (p < 0.05). Crystallinity increased up to 20% in extrudates with germinated flour compared to extrudates with ungerminated flour (EUG), observing changes at the molecular level by FTIR that impact the thermal and pasting properties. X-ray diffraction revealed angles of 2θ = 11.31, 16.60, 19.91, and 33.04 as a result of the germination and extrusion processes. Microstructural analysis indicated starch-protein interactions influencing changes in calorimetry, viscosity, X-ray diffraction, and digestibility. PCA allowed establishing that the addition of germinated flours significantly affected the properties and microstructural characteristics of extruded products, potentially affecting digestibility and nutritional quality.
Assuntos
Digestão , Germinação , Lupinus , Amido , Difração de Raios X , Zea mays , Zea mays/química , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Lupinus/química , Lupinus/metabolismo , Lupinus/crescimento & desenvolvimento , Amido/química , Amido/metabolismo , Farinha/análise , Viscosidade , Sementes/química , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Manipulação de AlimentosRESUMO
The synthesis, crystallization and characterization of a tri-fluoro-methane-sulfonate salt of 5,10,15,20-tetra-kis-(1-benzyl-pyridin-1-ium-4-yl)-21H,23H-por-phy-rin, C68H54N8 4+·4CF3SO3 -·4H2O, 1·OTf, are reported in this work. The reaction between 5,10,15,20-tetra-kis-(pyridin-4-yl)-21H,23H-porphyrin and benzyl bromide in the presence of 0.1 equiv. of Ca(OH)2 in CH3CN under reflux with an N2 atmosphere and subsequent treatment with silver tri-fluoro-methane-sulfonate (AgOTf) salt produced a red-brown solution. This reaction mixture was filtered and the solvent was allowed to evaporate at room temperature for 3â d to give 1·OTf. Crystal structure determination by single-crystal X-ray diffraction (SCXD) revealed that 1·OTf crystallizes in the space group P21/c. The asymmetric unit contains half a porphyrin mol-ecule, two tri-fluoro-methane-sulfonate anions and two water mol-ecules of crystallization. The macrocycle of tetra-pyrrole moieties is planar and unexpectedly it has coordinated CaII ions in occupational disorder. This CaII ion has only 10% occupancy (C72H61.80Ca0.10F12N8O16S4). The pyridinium rings bonded to methyl-ene groups from porphyrin are located in two different arrangements in almost orthogonal positions between the plane formed by the porphyrin and the pyridinium rings. The crystal structure features cationâ¯π inter-actions between the CaII atom and the π-system of the phenyl ring of neighboring mol-ecules. Both tri-fluoro-methane-sulfonate anions are found at the periphery of 1, forming hydrogen bonds with water mol-ecules.
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BACKGROUND: Gestational weight gain below or above the Institute of Medicine recommendations has been associated with adverse perinatal and neonatal outcomes. Very few studies have evaluated the association between serum and red blood cell folate concentrations and gestational weight gain in adolescents. Additionally, zinc deficiency during pregnancy has been associated with impaired immunity, prolonged labor, preterm and post-term birth, intrauterine growth restriction, low birth weight, and pregnancy-induced hypertension. OBJECTIVE: The purpose of our study is to evaluate the association between serum concentrations of zinc, serum folate, and red blood cell folate, with the increase in gestational weight and the weight and length of the newborn in a group of adolescent mothers from Mexico City. RESULTS: In our study, 406 adolescent-neonate dyads participated. The adolescents' median age was 15.8 years old. The predominant socioeconomic level was middle-low (57.8%), single (57%), 89.9% were engaged in home activities, and 41.3% completed secondary education. Excessive gestational weight gain was observed in 36.7% of cases, while insufficient gestational weight gain was noted in 38.4%. Small for gestational age infants were observed in 20.9% of the sample. Low serum folate (OR 2.1, 95% CI 1.3-3.3), decreased red blood cell folate (OR 1.6, 95% CI 1.0-2.6), and reduced serum zinc concentrations (OR 3.3, 95% CI 2.1-5.2) were associated with insufficient gestational weight gain. Decreased serum zinc levels (OR 1.2, 95% CI 1.2-3.4) were linked to an increased probability of delivering a baby who is small for their gestational age. CONCLUSIONS: Low serum folate, red blood cell folate, and serum zinc concentrations were associated with gestational weight gain and having a small gestational age baby. Both excessive and insufficient gestational weight gain, as well as having a small gestational age baby, are frequent among adolescent mothers.
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Peso ao Nascer , Eritrócitos , Ácido Fólico , Ganho de Peso na Gestação , Zinco , Humanos , Feminino , Zinco/sangue , Zinco/deficiência , Adolescente , Gravidez , Ácido Fólico/sangue , Recém-Nascido , México , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Gravidez na Adolescência/sangueRESUMO
Urinary tract infections (UTIs) caused by multidrug-resistant and extended-spectrum ß-lactamase-producing uropathogenic Escherichia coli are a worldwide concern. We report the draft genome of E. coli U13824 isolated from a female outpatient with UTI. This genome's availability strengthens the genomic surveillance of antimicrobial resistance and the spreading of these strains.
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Selective recognition of fructosyl amino acids in water by arylboronic acid-based receptors is a central field of modern supramolecular chemistry that impacts biological and medicinal chemistry. Fructosyl valine (FV) and fructosyl glycyl histidine (FGH) occur as N-terminal moieties of human glycated hemoglobin; therefore, the molecular design of biomimetic receptors is an attractive, but very challenging goal. Herein, we report three novel cationic Zn-terpyridine complexes bearing a fluorescent N-quinolinium nucleus covalently linked to three different isomers of strongly acidified phenylboronic acids (ortho-, 2Zn; meta-, 3Zn and para-, 4Zn) for the optical recognition of FV, FGH and comparative analytes (D-fructose, Gly, Val and His) in pure water at physiological pH. The complexes were designed to act as fluorescent receptors using a cooperative action of boric acid and a metal chelate. Complex 3Zn was found to display the most acidic -B(OH)2 group (pKa = 6.98) and exceptionally tight affinity for FV (K = 1.43 × 105 M-1) with a strong quenching analytical response in the micromolar concentration range. The addition of fructose and the other amino acids only induced moderate optical changes. On the basis of several spectroscopic tools (1H, 11B NMR, UV-Vis, and fluorescence titrations), ESI mass spectrometry, X-ray crystal structure, and DFT calculations, the interaction mode between 3Zn and FV is proposed in a 1 : 1 model through a cooperative two-point recognition involving a sp3 boronate-diol esterification with simultaneous coordination bonding of the carboxylate group of Val to the Zn atom. Fluorescence quenching is attributed to a static complexation photoinduced electron transfer mechanism as evidenced by lifetime experiments. The addition of FGH to 3Zn notably enhanced its emission intensity with micromolar affinity, but with a lower apparent binding constant than that observed for FV. FGH interacts with 3Zn through boronate-diol complexation and coordination of the imidazole ring of His. DFT-optimized structures of complexes 3Zn-FV and 3Zn-FGH show a picture of binding which shows that the Zn-complex has a suitable (Bâ¯Zn) distance to the two-point recognition with these analytes. Molecular recognition of fructosyl amino acids by transition-metal-based receptors has not been explored until now.
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Ácidos Borônicos , Complexos de Coordenação , Corantes Fluorescentes , Piridinas , Água , Zinco , Zinco/química , Ácidos Borônicos/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Piridinas/química , Água/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Valina/química , Estrutura Molecular , Histidina/químicaRESUMO
Breast cancer is the most common malignancy in women around the world. Intratumor and intertumoral heterogeneity persist in mammary tumors. Therefore, the identification of biomarkers is essential for the treatment of this malignancy. This study analyzed 28,143 genes expressed in 49 breast cancer cell lines using a Weighted Gene Co-expression Network Analysis to determine specific target proteins for Basal A, Basal B, Luminal A, Luminal B, and HER2 ampl breast cancer subtypes. Sixty-five modules were identified, of which five were characterized as having a high correlation with breast cancer subtypes. Genes overexpressed in the tumor were found to participate in the following mechanisms: regulation of the apoptotic process, transcriptional regulation, angiogenesis, signaling, and cellular survival. In particular, we identified the following genes, considered as hubs: IFIT3, an inhibitor of viral and cellular processes; ETS1, a transcription factor involved in cell death and tumorigenesis; ENSG00000259723 lncRNA, expressed in cancers; AL033519.3, a hypothetical gene; and TMEM86A, important for regulating keratinocyte membrane properties, considered as a key in Basal A, Basal B, Luminal A, Luminal B, and HER2 ampl breast cancer subtypes, respectively. The modules and genes identified in this work can be used to identify possible biomarkers or therapeutic targets in different breast cancer subtypes.