RESUMO
BACKGROUND: Early exercise for acute deep venous thrombosis (DVT) improves the patient's symptoms and does not increase the risk of pulmonary embolism. However, information about its effect on thrombus resolution is limited. The aim of this study was to investigate the role of resistance exercise (RE) in thrombus resolution and recanalization and determine its underlying mechanisms. METHODS: Ninety-six C57BL/6 J mice were randomly divided into four groups: Control group (C, n = 24); DVT group (D, n = 24); RE + DVT group (ED, n = 24); and inhibitor + RE + DVT group (IED, n = 24). A DVT model was induced by stenosis of the inferior vena cava (IVC). After undergoing IVC ultrasound within 24 h post-operation to confirm DVT formation, mice without thrombosis were excluded. Other mice were sacrificed and specimens were obtained 14 or 28 days after operation. Thrombus-containing IVC was weighed, and the thrombus area and recanalization rate were calculated using HE staining. Masson's trichrome staining was used to analyze the collagen content. RT-PCR and ELISA were performed to examine IL-6, TNF-α, IL-10, and VEGF expression levels. SIRT1 expression was assessed using immunohistochemistry staining and RT-PCR. VEGF-A protein expression and CD-31-positive microvascular density (MVD) in the thrombus were observed using immunohistochemistry. RESULTS: RE did not increase the incidence of pulmonary embolism. It reduced the weight and size of the thrombus and the collagen content. Conversely, it increased the recanalization rate. It also decreased the levels of the pro-inflammatory factors IL-6 and TNF-α and increased the expression levels of the anti-inflammatory factor IL-10. RE enhanced VEGF and SIRT1 expression levels and increased the MVD in the thrombosis area. After EX527 (SIRT1 inhibitor) was applied, the positive effects of exercise were suppressed. CONCLUSIONS: RE can inhibit inflammatory responses, reduce collagen deposition, and increase angiogenesis in DVT mice, thereby promoting thrombus resolution and recanalization. Its underlying mechanism may be associated with the upregulation of SIRT1 expression.
Assuntos
Condicionamento Físico Animal , Embolia Pulmonar , Treinamento Resistido , Trombose Venosa , Animais , Humanos , Camundongos , Colágeno/metabolismo , Modelos Animais de Doenças , Interleucina-10 , Interleucina-6/metabolismo , Camundongos Endogâmicos C57BL , Embolia Pulmonar/complicações , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Trombose Venosa/etiologiaRESUMO
BACKGROUND: MiR-92a-3p and oxidative stress are associated with catheter-related thrombosis (CRT). As a kind of physical intervention, resistance exercise can effectively promote blood circulation. In this study, we investigated the roles of miR-92a-3p, oxidative stress and the P38 mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) pathway in CRT during resistance exercise. METHODS: The rat CRT model was used for resistance exercise intervention. Moreover, pathological changes from the right jugular vein to the right auricle were observed under an electron microscope. In addition, reactive oxygen species (ROS) production, malondialdehyde (MDA) activity and heme oxygenase (HO-1) level in rat serum were detected via ELISA. The expression levels of miR-92A-3p and HO-1 in the vascular tissues of the rats were determined via real-time quantitative PCR. Additionally, the expression levels of HO-1, NF-κB P65, p38MAPK and IκBa in the venous tissues of the rats were analysed by Western blot analysis. RESULTS: The pathological results showed that the thrombosis incidence rate in the CRT + RE group was lower than that in the CRT group. In the CRT group, the expression levels of ROS and MDA, which are markers related to oxidative stress in serum, significantly increased whilst the expression of HO-1 decreased. In the venous tissue, the expression of miR-92a-3p increased, the level of HO-1 decreased, the levels of p38MAPK and NF-κB p65 significantly increased but that of P-IκBa and IκBa significantly decreased. In the CRT + RE group, after administering the resistance exercise intervention, ROS production and MDA activity in serum significantly decreased, the expression level of HO-1 increased and the expression level of miR-92a-3p in the venous tissues significantly decreased and was negatively correlated with that of HO-1. The levels of p38MAPK and NF-κB p65 significantly decreased but that of P- IκBa and IκBa significantly increased. CONCLUSION: Resistance exercise intervention downregulated miR-92a-3p expression, repaired oxidative stress injury and prevented CRT formation.
Assuntos
Coagulação Sanguínea , Cateterismo Venoso Central/efeitos adversos , Veias Jugulares/enzimologia , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Treinamento Resistido , Lesões do Sistema Vascular/terapia , Trombose Venosa/prevenção & controle , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Veias Jugulares/lesões , Veias Jugulares/patologia , Masculino , MicroRNAs/genética , Ratos Sprague-Dawley , Transdução de Sinais , Lesões do Sistema Vascular/enzimologia , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/patologia , Trombose Venosa/sangue , Trombose Venosa/enzimologia , Trombose Venosa/genéticaRESUMO
Alginate oligosaccharides (AOS) are divided by their monomer sequences into three types: oligomannuronate (MAOS), oligoguluronate (GAOS), and heterogeneous AOS (HAOS). However, how these AOS structures differentially regulate health and modulate gut microbiota is unclear. We explored the structure-function relationship of AOS both in an in vivo colitis model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged cell model. We found that MAOS administration significantly alleviated the symptom of experimental colitis and improved the gut barrier function in vivo and in vivo. Nevertheless, HAOS and GAOS were less effective than MAOS. The abundance and diversity of gut microbiota are obviously increased by MAOS intervention, but not by HAOS or GAOS. Importantly, microbiota from MAOS-dosed mice through FMT decreased the disease index level, alleviated histopathological changes, and improved gut barrier function in the colitis model. Super FMT donors induced by MAOS but not by HAOS or GAOS, seemed to exert potential in colitis bacteriotherapy. These findings may aid in establishing precise pharmaceutical applications based on the targeted production of AOS.
Assuntos
Colite , Microbioma Gastrointestinal , Animais , Camundongos , Alginatos/farmacologia , Alginatos/uso terapêutico , Sulfato de Dextrana/toxicidade , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Oligossacarídeos/farmacologia , Oligossacarídeos/uso terapêutico , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , ColoRESUMO
Alginate oligosaccharides (AOS) are degradation products of alginate extracted from brown algae. With low molecular weight, high water solubility, and good biological activity, AOS present anti-inflammatory, antimicrobial, antioxidant, and antitumor properties. They also exert growth-promoting effects in animals and plants. Three types of AOS, mannuronate oligosaccharides (MAOS), guluronate oligosaccharides (GAOS), and heterozygous mannuronate and guluronate oligosaccharides (HAOS), can be produced from alginate by enzymatic hydrolysis. Thus far, most studies on the applications and biological activities of AOS have been based mainly on a hybrid form of HAOS. To improve the directional production of AOS for practical applications, systematic studies on the structures and related biological activities of AOS are needed. This review provides a summary of current understanding of structure-function relationships and advances in the production of AOS. The current challenges and opportunities in the application of AOS is suggested to guide the precise application of AOS in practice.
Assuntos
Alginatos , Phaeophyceae , Alginatos/química , Animais , Antioxidantes , Oligossacarídeos/química , Phaeophyceae/metabolismo , Polissacarídeo-Liases/metabolismo , Relação Estrutura-AtividadeRESUMO
Chitosan oligosaccharides (COS) show the potential to support the intestinal health, but the mechanism and role of COS-derived intestinal microbiota are unknown. We explored the protective effect of direct administration of COS on intestinal barrier function using an in vivo colitis mouse model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged IPEC-J2 cell model. COS directly enhanced the intestinal barrier function. COS intervention also promoted the abundance and diversity of intestinal flora. Importantly, FMT intervention with a COS-derived microbiome decreased the disease index level and alleviated histopathological changes, and improved gut barrier function in the colitis model. Both COS and COS-derived microbiota suppressed ETEC-induced cellular apoptosis in IPEC-J2 cells. This study firstly confirms transplantation of COS-modified fecal microbiota can enhance the intestinal barrier function. The mechanism underlying COS benefits is due to a direct intervention by COS supplementation and an indirect improvement of the gut microbiota induced by COS exposure.
Assuntos
Quitosana , Colite , Escherichia coli Enterotoxigênica , Animais , Apoptose , Quitosana/efeitos adversos , Colite/induzido quimicamente , Mucosa Intestinal , Camundongos , Oligossacarídeos/farmacologiaRESUMO
Milk production and body conformation traits are critical economic traits for dairy cows. To understand the basic genetic structure for those traits, a genome wide association study was performed on milk yield, milk fat yield, milk fat percentage, milk protein yield, milk protein percentage, somatic cell score, body form composite index, daily capacity composite index, feed, and leg conformation traits, based on the Illumina Bovine HD100k BeadChip. A total of 57, 12 and 26 SNPs were found to be related to the milk production, somatic cell score and body conformation traits in the Holstein cattle. Genes with pleiotropic effect were also found in this study. Seven significant SNPs were associated with multi-traits and were located on the PLEC, PLEKHA5, TONSL, PTGER4, and LCORL genes. In addition, some important candidate genes, like GPAT3, CEBPB, AGO2, SLC37A1, and FNDC3B, were found to participate in fat metabolism or mammary gland development. These results can be used as candidate genes for milk production, somatic cell score, and body conformation traits of Holstein cows, and are helpful for further gene function analysis to improve milk production and quality.