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1.
Biology (Basel) ; 13(6)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38927262

RESUMO

Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT1R blockade has anti-inflammatory effects. The use of an AT1 receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT1 receptor gene silencing on the modulation of cytokines (e.g., IL-1ß, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. MATERIALS AND METHODS: We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT1R, NF-κB, and cytokines (IL-1ß, TNF-α, and IL-10) were measured by RT-qPCR. RESULTS: We observed that silencing of the AT1 receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1ß and TNF-α), NF-κB, and PPAR-γ. CONCLUSIONS: We conclude that AT1R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1ß via NF-κB in macrophages and having high blood pressure decrease.

2.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38399437

RESUMO

Previous studies provided evidence of the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on the cardiovascular system and inflammation. However, its possible effect on skeletal muscle is unknown. This study aimed to evaluate whether ω-3 PUFA reverses the dysregulation of metabolic modulators in the skeletal muscle of rats on a high-fat obesogenic diet. For this purpose, an animal model was developed using male Wistar rats with a high-fat diet (HFD) and subsequently supplemented with ω-3 PUFA. Insulin resistance was assessed, and gene and protein expression of metabolism modulators in skeletal muscle was also calculated using PCR-RT and Western blot. Our results confirmed that in HFD rats, zoometric parameters and insulin resistance were increased compared to SD rats. Furthermore, we demonstrate reduced gene and protein expression of peroxisome proliferator-activated receptors (PPARs) and insulin signaling molecules. After ω-3 PUFA supplementation, we observed that glucose (24.34%), triglycerides (35.78%), and HOMA-IR (40.10%) were reduced, and QUICKI (12.16%) increased compared to HFD rats. Furthermore, in skeletal muscle, we detected increased gene and protein expression of PPAR-α, PPAR-γ, insulin receptor (INSR), insulin receptor substrate 1 (ISR-1), phosphatidylinositol-3-kinase (PI3K), and glucose transporter 4 (GLUT-4). These findings suggest that ω-3 PUFAs decrease insulin resistance of obese skeletal muscle.

3.
Nutrients ; 16(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38337625

RESUMO

Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.


Assuntos
Asma , MicroRNAs , Humanos , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , MicroRNAs/genética , Remodelação das Vias Aéreas , Asma/tratamento farmacológico , Asma/genética , Asma/complicações , Pulmão , Inflamação/complicações , Suplementos Nutricionais
4.
Biomedicines ; 11(9)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37760864

RESUMO

Prompt diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for initiating timely treatment. MicroRNAs have recently emerged as biomarkers in cardiovascular diseases. This study aimed to evaluate the discriminatory capacity of serum microRNAs in identifying an ischemic origin in patients presenting with chest discomfort to the Emergency Department. The study included 98 participants (78 with STEMI and 20 with nonischemic chest discomfort). Significant differences in the expression levels of miR-133b, miR-126, and miR-155 (but not miR-1, miR-208, and miR-208b) were observed between groups. miR-133b and miR-155 exhibited 97% and 93% sensitivity in identifying STEMI patients, respectively. miR-126 demonstrated a specificity of 90% in identifying STEMI patients. No significant associations were found between microRNAs and occurrence of major adverse cardiovascular events (MACE). However, patients with MACE had higher levels of interleukin (IL)-15, IL-21, IFN-γ-induced protein-10, and N-terminal pro B-type natriuretic peptide compared to non-MACE patients. Overall, there were significant associations among the expression levels of microRNAs. However, microRNAs did not demonstrate associations with either inflammatory markers or cardiovascular risk scores. This study highlights the potential of microRNAs, particularly miR-133b and miR-126, as diagnostic biomarkers for distinguishing patients with STEMI from those presenting with nonischemic chest discomfort to the Emergency Department.

5.
Int J Mol Sci ; 24(14)2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37510995

RESUMO

Glycine is a non-essential amino acid with many functions and effects. Glycine can bind to specific receptors and transporters that are expressed in many types of cells throughout an organism to exert its effects. There have been many studies focused on the anti-inflammatory effects of glycine, including its abilities to decrease pro-inflammatory cytokines and the concentration of free fatty acids, to improve the insulin response, and to mediate other changes. However, the mechanism through which glycine acts is not clear. In this review, we emphasize that glycine exerts its anti-inflammatory effects throughout the modulation of the expression of nuclear factor kappa B (NF-κB) in many cells. Although glycine is a non-essential amino acid, we highlight how dietary glycine supplementation is important in avoiding the development of chronic inflammation.


Assuntos
Glicina , Oligoelementos , Humanos , Glicina/farmacologia , Glicina/uso terapêutico , Micronutrientes/uso terapêutico , Citocinas/metabolismo , NF-kappa B/metabolismo , Aminoácidos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Oligoelementos/uso terapêutico
6.
Nutrients ; 15(13)2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37447169

RESUMO

The human skin is a crucial organ that protects the organism from the outer environment. Skin integrity and health depend on both extrinsic and intrinsic factors. Intrinsic factors such as aging and genetic background contribute to weakened skin and disease susceptibility. Meanwhile, extrinsic factors including UV radiation, pollution, smoking, humidity, and poor diet also affect skin health and disease. On the other hand, healthy dietary patterns such as plant-based diets have gained popularity as a complementary therapy for skin health. A plant-based diet is defined as all diets based on plant foods, including an abundance of vegetables, fruits, beans, lentils, legumes, nuts, seeds, fungi, and whole grains, with limited or no animal products or processed foods. However, some authors also exclude or limit processed foods in the definition. Recent research has shown that these diets have beneficial effects on inflammatory skin diseases. This review explored the beneficial effects of plant-based diets on inflammatory skin diseases and plant-based functional foods on healthy skin. In conclusion, plant-based diets and plant-based functional foods may have beneficial effects on skin health through the gut microbiome.


Assuntos
Dermatite , Dieta Vegetariana , Humanos , Dieta , Verduras , Plantas
7.
Int J Mol Sci ; 24(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37047453

RESUMO

Asthma is a heterogeneous entity encompassing distinct endotypes and varying phenotypes, characterized by common clinical manifestations, such as shortness of breath, wheezing, and variable airflow obstruction. Two major asthma endotypes based on molecular patterns are described: type 2 endotype (allergic-asthma) and T2 low endotype (obesity-related asthma). Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides in length, currently involved in many diverse biological functions, such as chromatin remodeling, gene transcription, protein transport, and microRNA processing. Despite the efforts to accurately classify and discriminate all the asthma endotypes and phenotypes, if long noncoding RNAs could play a role as biomarkers in allergic asthmatic and adolescent obesity-related asthma, adolescents remain unknown. To compare expression levels of lncRNAs: HOTAIRM1, OIP5-AS1, MZF1-AS1, and GAS5 from whole blood of Healthy Adolescents (HA), Obese adolescents (O), allergic asthmatic adolescents (AA) and Obesity-related asthma adolescents (OA). We measured and compared expression levels from the whole blood of the groups mentioned above through RT-q-PCR. We found differentially expressed levels of these lncRNAs between the groups of interest. In addition, we found a discriminative value of previously mentioned lncRNAs between studied groups. Finally, we generated an interaction network through bioinformatics. Expression levels of OIP5-AS1, MZF1-AS1, HOTAIRM1, and GAS5 in whole blood from the healthy adolescent population, obese adolescents, allergic asthma adolescents, and obesity-related asthma adolescents are differently expressed. Moreover, these lncRNAs could act as molecular biomarkers that help to discriminate between all studied groups, probably through molecular mechanisms with several genes and miRNAs implicated.


Assuntos
Asma , MicroRNAs , Obesidade Infantil , RNA Longo não Codificante , Adolescente , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Obesidade Infantil/complicações , Obesidade Infantil/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Asma/genética , Biomarcadores , Proliferação de Células/genética , Fatores de Transcrição Kruppel-Like
8.
Life (Basel) ; 12(11)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36362842

RESUMO

BACKGROUND: Chronic or low-grade inflammation is a process where various immune cells are recruited from the periphery into adipose tissue. This event gives rise to localised inflammation, in addition to having a close interaction with cardiometabolic pathologies where the mediation of orphan receptors is observed. The aim of this study was to analyse the participation of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in a chronic inflammatory process in 3T3-L1 cells. The 3T3-L1 cells were stimulated with TNF-α (5 ng/mL) for 60 min as an inflammatory model. Gene expression was measured by RT-qPCR. RESULTS: We showed that the inflammatory stimulus of TNF-α in adipocytes decreased the expression of the orphan receptors GPR21, GPR26, GPR39, GPR82 and GPR6, which are related to low-grade inflammation. CONCLUSIONS: Our results suggest that GPR21 and GPR82 are modulated by glycine, it shows a possible protective role in the presence of an inflammatory environment in adipocytes, and they could be a therapeutic target to decrease the inflammation in some diseases related to low-grade inflammation such as diabetes, obesity and metabolic syndrome.

9.
J Drug Target ; 30(6): 673-686, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35289235

RESUMO

Diabetes is a disease that leads to proliferative diabetic retinopathy (PDR), which is associated with an increase of new vessels formation due to an overexpression of angiogenic factors, such as angiopoietin 2 (ANGPT2). The aim of this work was to design a siRNA targeting ANGPT2 to decrease the retinal neovascularization associated with PDR. Adult male Wistar rats weighing 325-375 g were used. Diabetes was induced by a single dose of streptozotocin (STZ, 60 mg/kg i.p.). The siRNAs were designed, synthesised, and administered intravitreally at the beginning of diabetes induction (t0), and after 4 weeks of diabetes evolution (t4), subsequently evaluated the retinal neovascularization (junctions and lacunarity) and ANGPT2 expression in the retina by RT-PCR, after 4 weeks of the siRNAs administration. The results showed that the administration of STZ produced significant increases in blood glucose levels, retinal neovascularization (augmented junctions and lower lacunarity), and ANGPT2 expression, while the administration of the ANGPT2-siRNAs at different groups (t0 and t4) reduces the junctions and increases the lacunarity in diabetic rats. Therefore, we conclude that the administration of siRNAs targeting ANGPT2 could be an option to decrease the retinal neovascularization associated with PDR and halt the progression of blindness caused by diabetes.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Neovascularização Retiniana , Angiopoietina-2/genética , Animais , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/genética , Masculino , Neovascularização Patológica/genética , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Wistar , Retina/metabolismo , Neovascularização Retiniana/complicações , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Estreptozocina
10.
Mol Cell Biochem ; 477(4): 1309-1320, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35138512

RESUMO

The prevalence of the metabolic syndrome (MetS) and its cardiac comorbidities as cardiac hypertrophy (CH) have increased considerably due to the high consumption of carbohydrates, such as sucrose and/or fructose. We compared the effects of sucrose (S), fructose (F) and their combination (S + F) on the development of MetS in weaned male Wistar rats and established the relationship between the consumption of these sugars and the degree of cardiac CH development, oxidative stress (OS) and Calcium/calmodulin-dependent protein kinase type II subunit delta oxidation (ox-CaMKIIδ). 12 weeks after the beginning of treatments with S, F or S + F, arterial pressure was measured and 8 weeks later (to complete 20 weeks) the animals were sacrificed and blood samples, visceral adipose tissue and hearts were obtained. Biochemical parameters were determined in serum and cardiac tissue to evaluate the development of MetS and OS. To evaluate CH, atrial natriuretic peptide (ANP), CaMKIIδ and ox-CaMKIIδ were determined by western blot and histological studies were performed in cardiac tissue. Our data showed that chronic consumption of S + F exacerbates MetS-induced CH which is related with a higher OS and ox-CaMKIIδ.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomegalia/enzimologia , Carboidratos da Dieta/efeitos adversos , Frutose/efeitos adversos , Síndrome Metabólica/enzimologia , Miocárdio/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Sacarose/efeitos adversos , Animais , Carboidratos da Dieta/farmacologia , Frutose/farmacologia , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Ratos Wistar , Sacarose/farmacologia
11.
Heliyon ; 8(12): e12316, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36590520

RESUMO

A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of RORC, IL17A, and TNFA. However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between RORC, IL17A, and TNFA methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11-18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of RORC, IL17A, and TNFA than the HP group. Notably, the OAP group presents lower RORC promoter methylation status than the OP group. Interestingly, RORC promoter methylation status was moderately negatively associated with gene expression of RORC (r s = -0.39, p < 0.001) and IL17A (r s = -0.37, p < 0.01), respectively. Similarly, the promoter methylation pattern of IL17A was moderately negatively correlated with IL17A gene expression (r s = -0.3, p < 0.01). There is also a moderate inverse relationship between TNFA promoter methylation status and TNFA gene expression (r s = -0.3, p < 0.01). The present study suggests an association between lower RORC, IL17A, and TNFA gene promoter methylation status with obesity-related asthma and allergic asthma. RORC, IL17A, and TNFA gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate RORC, IL17A, and TNF gene expression in both asthmatic phenotypes.

12.
Nutrients ; 13(12)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34959795

RESUMO

We investigated if supplementing obese mothers (MO) with docosahexaenoic acid (DHA) improves milk long-chain polyunsaturated fatty acid (LCPUFA) composition and offspring anxiety behavior. From weaning throughout pregnancy and lactation, female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating and through lactation, half the mothers received 400 mg DHA kg-1 d-1 orally (C+DHA or MO+DHA). Offspring ate C after weaning. Maternal weight, total body fat, milk hormones, and milk nutrient composition were determined. Pups' milk nutrient intake was evaluated, and behavioral anxiety tests were conducted. MO exhibited increased weight and total fat, and higher milk corticosterone, leptin, linoleic, and arachidonic acid (AA) concentrations, and less DHA content. MO male and female offspring had higher ω-6/ ω-3 milk consumption ratios. In the elevated plus maze, female but not male MO offspring exhibited more anxiety. MO+DHA mothers exhibited lower weight, total fat, milk leptin, and AA concentrations, and enhanced milk DHA. MO+DHA offspring had a lower ω-6/ω-3 milk intake ratio and reduced anxiety vs. MO. DHA content was greater in C+DHA milk vs. C. Supplementing MO mothers with DHA improves milk composition, especially LCPUFA content and ω-6/ω-3 ratio reducing offspring anxiety in a sex-dependent manner.


Assuntos
Animais Recém-Nascidos/psicologia , Comportamento Animal/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Leite/química , Animais , Ansiedade/prevenção & controle , Ingestão de Alimentos/psicologia , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/análise , Ácidos Graxos Insaturados/análise , Feminino , Lactação , Masculino , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Obesidade , Gravidez , Ratos , Ratos Wistar , Fatores Sexuais
13.
Allergol Immunopathol (Madr) ; 49(3): 21-29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33938185

RESUMO

BACKGROUND: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. OBJECTIVE: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. METHODS: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). RESULTS: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8-76.0] vs. 23.5 ng/mL [95% CI: 3.2-33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7-26.5] vs. 15.9 ng/mL [95% CI: 9.4-18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599-0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554-0.819, p = 0.008), considered fair. CONCLUSIONS: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice.


Assuntos
Asma/sangue , Obesidade Infantil/complicações , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Adolescente , Asma/etiologia , Biomarcadores/sangue , Índice de Massa Corporal , Criança , Intervalos de Confiança , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade Infantil/sangue , Prognóstico , Curva ROC
14.
Inflamm Res ; 70(5): 605-618, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33877377

RESUMO

OBJECTIVE: To determine the involvement of TNF-α and glycine receptors in the inhibition of pro-inflammatory adipokines in 3T3-L1 cells. METHODS: RT-PCR evidenced glycine receptors in 3T3-L1 adipocytes. 3T3-L1 cells were transfected with siRNA for the glycine (Glrb) and TNF1a (Tnfrsf1a) receptors and confirmed by confocal microscopy. Transfected cells were treated with glycine (10 mM). The expressions of TNF-α and IL-6 mRNA were measured by qRT-PCR, while concentrations were quantified by ELISA. RESULTS: Glycine decreased the expression and concentration of TNF-α and IL-6; this effect did not occur in the absence of TNF-α receptor due to siRNA. In contrast, glycine produced only slight changes in the expression of TNF-α and IL-6 in the absence of the glycine receptor due to siRNA. A docking analysis confirmed the possibility of binding glycine to the TNF-α1a receptor. CONCLUSION: These findings support the idea that glycine could partially inhibit the binding of TNF-α to its receptor and provide clues about the mechanisms by which glycine inhibits the secretion of pro-inflammatory adipokines in adipocytes through the TNF-α receptor.


Assuntos
Adipócitos/metabolismo , Citocinas/metabolismo , Glicina/farmacologia , Receptores Tipo II do Fator de Necrose Tumoral/antagonistas & inibidores , Receptores Tipo I de Fatores de Necrose Tumoral/antagonistas & inibidores , Células 3T3-L1 , Adiponectina/genética , Animais , Citocinas/genética , Expressão Gênica , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Receptores de Glicina/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética
15.
Clin Immunol ; 229: 108715, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33771687

RESUMO

Obesity is associated with a unique non-T2 asthma phenotype, characterised by a Th17 immune response. Retinoid-related orphan receptor C (RORC) is the master transcription factor for Th17 polarisation. We investigated the association of TNFA, IL17A, and RORC mRNA expression levels with the non-T2 phenotype. We conducted a cross-sectional study in adolescents, subdivided as follows: healthy (HA), allergic asthma without obesity (AA), obesity without asthma (OB), and non-allergic asthma with obesity (NAO). TNFA, IL17A, and RORC mRNA expression in peripheral blood leukocytes were assessed by RT-PCR. NAO exhibited higher TNFA mRNA expression levels than HA or OB, as well as the highest IL17A and RORC mRNA expression levels among the four groups. The best biomarker for discriminating non-allergic asthma among obese adolescents was RORC mRNA expression levels (area under the curve: 0.95). RORC mRNA expression levels were associated with the non-T2 asthma phenotype, hinting at a therapeutic target in obesity-related asthma.


Assuntos
Asma/complicações , Asma/imunologia , Interleucina-17/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Obesidade/complicações , Obesidade/imunologia , RNA Mensageiro/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Asma/genética , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Expressão Gênica , Humanos , Interleucina-17/sangue , Leucócitos/imunologia , Masculino , Obesidade/genética , Fenótipo , RNA Mensageiro/sangue , Células Th17/imunologia , Fator de Necrose Tumoral alfa/sangue
17.
Med Hypotheses ; 144: 109935, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32795834

RESUMO

Coronavirus disease 2019 (COVID-19) was declared a pandemic and international health emergency by the World Health Organization. Patients with obesity with COVID-19 are 7 times more likely to need invasive mechanical ventilation than are patients without obesity (OR 7.36; 95% CI: 1.63-33.14, p = 0.021). Acute respiratory distress syndrome (ARDS) is one of the main causes of death related to COVID-19 and is triggered by a cytokine storm that damages the respiratory epithelium. Interleukins that cause the chronic low-grade inflammatory state of obesity, such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant peptide (MCP)-1, and, in particular, IL-17A and tumour necrosis factor alpha (TNF-α), also play very important roles in lung damage in ARDS. Therefore, obesity is associated with an immune state favourable to a cytokine storm. Our hypothesis is that serum concentrations of TNF-α and IL-17A are more elevated in patients with obesity and COVID-19, and consequently, they have a greater probability of developing ARDS and death. The immunobiology of IL-17A and TNF-α opens a new fascinating field of research for COVID-19.


Assuntos
COVID-19/complicações , Interleucina-17/sangue , Obesidade/complicações , Síndrome do Desconforto Respiratório/etiologia , Fator de Necrose Tumoral alfa/sangue , Biomarcadores/sangue , COVID-19/imunologia , COVID-19/mortalidade , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Humanos , Modelos Imunológicos , Obesidade/imunologia , Pandemias , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/mortalidade , Mucosa Respiratória/imunologia , Mucosa Respiratória/lesões , Fatores de Risco
18.
Med Hypotheses ; 134: 109527, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31877441

RESUMO

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.


Assuntos
Asma/etiologia , Metilação de DNA , Interleucina-17/genética , Modelos Imunológicos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Obesidade/complicações , Regiões Promotoras Genéticas , Células Th17/metabolismo , Fator de Necrose Tumoral alfa/genética , Tecido Adiposo/metabolismo , Adolescente , Adulto , Animais , Asma/genética , Asma/imunologia , Causalidade , Criança , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação , Interleucina-23/fisiologia , Macrófagos/metabolismo , Masculino , Metanálise como Assunto , Camundongos , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/fisiologia , Obesidade/imunologia , Fator de Necrose Tumoral alfa/fisiologia
19.
J Vasc Res ; 57(1): 1-7, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31266033

RESUMO

Metabolic syndrome (MS) is a clinical condition, constituted by alterations that lead to the onset of type II diabetes and cardiovascular disease. It has been reported that orphan G-protein-coupled receptor 82 (GPR82) participates in metabolic processes. The aim of this study was to evaluate the function of GPR82 in MS using a small interfering RNA (siRNA) against this receptor. We used Wistar rats of 10-12 weeks of age fed with a high-fructose solution (70%) for 9 weeks to induce MS. Subsequently, the rats were treated with an intrajugular dose of an siRNA against GPR82 and the effects were evaluated on day 3 and 7 after administration. On day 3 the siRNA had a transient effect on decreasing blood pressure and triglycerides and increasing high-density lipoprotein cholesterol, which recovered to the MS control on day 7. Decreased gene expressions of GPR82 mRNA in the aorta and heart were observed on day 3; moreover, decreased gene expression was maintained in the aorta on day 7. Therefore, we conclude that the orphan receptor GPR82 participates in the development of MS induced by fructose and the silencing of this receptor could ameliorate metabolic components.


Assuntos
Frutose/administração & dosagem , Síndrome Metabólica/etiologia , Receptores Acoplados a Proteínas G/fisiologia , Animais , Carboidratos da Dieta/administração & dosagem , Masculino , Interferência de RNA , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/genética , Sístole , Triglicerídeos/sangue
20.
Horiz. sanitario (en linea) ; 18(2): 139-148, may.-ago. 2019. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1039981

RESUMO

Resumen: Objetivo: Identificar y analizar desde una perspectiva cuanti/cualitativita los indicadores socioeconómicos de la obesidad materna en México. Material y métodos: Investigación evaluativa basada en un diseño de cohorte de tipo prospectivo/descriptivo. El tamaño de la muestra se conformó por todas las mujeres que llegaron a consulta prenatal a partir de la semana 24 de gestación en un hospital de referencia estatal. El tamaño de la muestra se estimó con un 80% de poder y 95% de confianza y significancia. Los indicadores de interés fueron aspectos socioeconómicos, alimentación, antropometría, dieta, seguridad alimentaria y actividad física. El análisis cuantitativo se realizó utilizando el software Stata versión 14 y el análisis cualitativo con Atlas-ti versión 8.0. Resultados: La cohorte estuvo conformada por 402 mujeres embarazadas en 2017. De los resultados principales encontramos que el 55% de las mujeres se encontraba en el rango de edad de 18-24 años; el 15% de las mujeres refirió contar con un empleo remunerado; el 42% de la población tenía secundaria completa; el 32.1% presentó un grado de inseguridad alimentaria; la media de IMC fue de 27.8±4.8, el 48% de las mujeres presentaron sobrepeso y obesidad. Conclusiones: Los resultados cuantitativos sugieren que poblaciones con mayor vulnerabilidad socio-económica, inseguridad alimentaria y escasa actividad física, son más propensas a la obesidad materna. Los resultados cualitativos, además de complementar y reforzar los resultados cuantitativos, plantean evidencias para identificar a mayor detalle las barreras y facilitadores para fortalecer programas de intervención en la prevención de la obesidad materna.


Abstract; Objective: To identify and analyze from a quantitative / qualitative perspective the socioeconomic indicators of maternal obesity in Mexico. Methods and material: Evaluative research based on a prospective / analytical cohort design. The sample size was established by all the women who came to the antenatal clinic from the 24th week of gestation in a state referral hospital. The sample size was estimated with 80% power and 95% confidence and significance. The indicators of interest were socioeconomic aspects, nutrition, anthropometry, diet, food safety and physical activity. The quantitative analysis was performed using the Stata version 14 software and the qualitative analysis with Atlas-ti version 8.0. Results: The cohort was comprised of 402 pregnant women in 2017. From the main results we found that 55% of the women were in the age range of 18-24 years; 15% of women reported having a paid job; 42% of the population had full secondary education; 32.1% presented a degree of food insecurity; the mean BMI was 27.8 ± 4.8, 48% of the women were overweight and obese. Conclusions: Quantitative results suggest that populations with greater socio-economic vulnerability, food insecurity and low physical activity are more prone to maternal obesity. The qualitative results, besides complementing and reinforcing the quantitative results, present evidence to identify in greater detail the barriers and facilitators to strengthen intervention programs in the prevention of maternal obesity.


Resumo: Objetivo: Identificar e analisar, de uma perspectiva quantitativa / qualitativa, os indicadores socioeconômicos da obesidade materna no México. Materiais e métodos: Pesquisa avaliativa baseada em um desenho de coorte prospectivo / analítico. O tamanho da amostra foi estabelecido por todas as mulheres que chegaram à clínica pré-natal a partir da 24a semana de gestação em um hospital estadual de referência. O tamanho da amostra foi estimado com 80% de poder e 95% de confiança e significância. Os indicadores de interesse foram aspectos socioeconómicos, nutrição, antropometria, dieta, segurança alimentar e atividade física. A análise quantitativa foi realizada utilizando o software Stata versão 14 e a análise qualitativa com Atlas-ti versão 8.0. Resultados: A coorte foi composta por 402 gestantes em 2017. Dos principais resultados, constatou-se que 55% das mulheres encontravam- se na faixa etária de 18 a 24 anos; 15% das mulheres relataram ter um emprego remunerado; 42% da população tinha ensino secundário completo; 32,1% apresentaram grau de insegurança alimentar; a média do IMC foi de 27,8 ± 4,8, 48% das mulheres estavam acima do peso e obesas. Conclusões: Os resultados quantitativos sugerem que populações com maior vulnerabilidade socioeconómica, insegurança alimentar e baixa atividade física são mais propensas à obesidade materna. Os resultados qualitativos, além de complementar e reforjar os resultados quantitativos, apresentam evidencias para identificar em maior detalhe as barreiras e facilitadores para fortalecer os programas de intervenção na prevenção da obesidade materna.


Résumé: Objectif: Identifier et analyser d'un point de vue quantitatif / qualitatif les indicateurs socio-économiques de l'obésité maternelle au Mexique. Matériel et méthodes: Recherche évaluative basée sur une conception de cohorte prospective / analytique. La taille de l'échantillon a été établie par toutes les femmes qui sont venues á la clinique prénatale á partir de la 24e semaine de gestation dans un hópital de référence. La taille de l'échantillon a été estimée avec 80% de puissance et 95% de confiance et de signification. Les indicateurs d'intéret étaient les aspects socio-économiques, la nutrition, l'anthropométrie, l'alimentation, la sécurité alimentaire et l'activité physique. L'analyse quantitative a été réalisée á l'aide du logiciel Stata version 14 et de l'analyse qualitative avec Atlas-ti version 8.0. Résultats: La cohorte était composée de 402 femmes enceintes en 2017. D'aprés les principaux résultats, nous avons constaté que 55% des femmes étaient agées de 18 á 24 ans; 15% des femmes ont déclaré avoir un travail rémunéré; 42% de la population ont fait des études secondaires complétes; 32,1% présentaient un degré d'insécurité alimentaire; l'IMC moyen était de 27,8 ± 4,8, 48% des femmes étaient en surpoids et obéses. Conclusions: Les résultats quantitatifs suggérent que les populations ayant une plus grande vulnérabilité socio-économique, l'insécurité alimentaire et une faible activité physique sont plus sujettes á l'obésité maternelle. Les résultats qualitatifs, en plus de compléter et de renforcer les résultats quantitatifs, présentent des preuves pour identifier plus en détail les obstacles et les facilitateurs pour renforcer les programmes d'intervention dans la prévention de l'obésité maternelle.

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