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BACKGROUND: Atherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases. METHODS: Transcriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RStudio software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.Furthermore, the hub gene was screened by Cytoscape software, and the immune infiltration of hub gens was analyzed. Finally, relevant clinical blood samples were collected for qRT-PCR verification of the three most important hub genes. RESULTS: A total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by venn diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of the Protein-Protein Interaction(PPI) network and Cytoscape software analysis, we finally screened 10 hub genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test < 0.05), while in GSE98895, the infiltration scores of 4 kinds of immune cells were significantly different between groups (Wilcoxon Test < 0.05). Spearman method was used to analyze the correlation between the expression of 10 key genes and 22 kinds of immune cell infiltration scores in two data sets. The results showed that there were 42 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE28829 (|Cor| > 0.3 & P < 0.05). There were 41 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE98895 (|Cor| > 0.3 & P < 0.05). Finally, our results identified 10 small molecules with the highest absolute enrichment value, and the three most significant key genes (CX3CR1, TLR5, IL32) were further verified in the data expression matrix and clinical blood samples. CONCLUSION: We have established a co-expression network between atherosclerotic progression and metabolic syndrome, and identified key genes between the two diseases. Through the method of bioinformatics, we finally obtained 10 hub genes in As and MS, and selected 3 of the most significant genes (CX3CR1, IL32, TLR5) for blood PCR verification. This may be helpful to provide new research ideas for the diagnosis and treatment of AS complicated with MS.
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Aterosclerosis , Bases de Datos Genéticas , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Síndrome Metabólico , Mapas de Interacción de Proteínas , Humanos , Síndrome Metabólico/genética , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/inmunología , Aterosclerosis/genética , Aterosclerosis/inmunología , Aterosclerosis/diagnóstico , Aterosclerosis/sangre , Transcriptoma , Masculino , Valor Predictivo de las Pruebas , Marcadores Genéticos , Reproducibilidad de los Resultados , Predisposición Genética a la Enfermedad , Biología Computacional , Persona de Mediana Edad , Femenino , Regulación de la Expresión GénicaRESUMEN
Microbial fermented feed (MF) is considered a valuable strategy to bring advantages to livestock and is widely practiced. Oral supplementation of Ginseng polysaccharide (Gps) eliminated weight loss in chickens following vaccination. This study investigated the effects of the combined use of Gps and MF on growth performance and immune indices in Xuefeng black-bone chickens. A total of 400 Xuefeng black-bone chickens at the age of 1 day were randomly assigned to four groups. Normal feed group (Control group), ginseng polysaccharide (200 mg/kg) group (Gps group), microbially fermented feed (completely replace the normal feed) group (MF group), and microbially fermented feed and add ginseng polysaccharide just before use (MF + Gps group). Each group contained 5 pens per treatment and 20 birds per pen. The body weight and average daily gain in the Gps, MF, and MF + Gps groups increased significantly (P < 0.01), while the feed conversion ratio decreased significantly (P < 0.01). The combined use of MF and Gps showed a synergistic effect. There was no significant difference in villus height (cecal) between the experimental group and the Con group. The crypt depth of the three experimental groups exhibited a significantly lower value compared to the Control group (P < 0.05). The V/C ratio of the Gps group and MF + Gps was significantly increased (P < 0.05), but there was no significant difference in the MF group. Moreover, the diarrhea rate of the Gps and the MF + Gps groups was lower than that of the Con group, while that of the MF + Gps group decreased the mortality rate (P < 0.05). The serum tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) levels in the MF, Gps, and MF + Gps groups decreased significantly (P < 0.01), the serum immunoglobulin G (IgG) levels increased significantly (P < 0.01), while the combination of MF and Gps had a synergistic effect. The combined use of Gps and MF not only further improved growth performance and immune parameters, but also reduced the diarrhea rate and mortality.
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Panax , Animales , Pollos , Peso Corporal , Ciego , Diarrea/veterinariaRESUMEN
BACKGROUND: Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed. RESULTS: The results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05). CONCLUSIONS: These results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens.
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Alimentación Animal , Pollos , Dieta , Suplementos Dietéticos , Emulsionantes , Metabolismo de los Lípidos , Animales , Pollos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Emulsionantes/farmacología , Alimentación Animal/análisis , Masculino , Femenino , Dieta/veterinaria , Hígado/metabolismo , Hígado/efectos de los fármacosRESUMEN
Increasing studies have highlighted the significance of milk-derived extracellular vesicles (MEVs) in mother-newborn integration, as well as their application as novel drug delivery systems and diagnostic biomarkers. However, conventional ultracentrifugation (UC) often results in the co-precipitation of casein micelles in MEV pellets. In this study, we compared methods with different principles to screen the optimal pretreatment in caseins removal, and found that isoelectric precipitation by hydrochloric acid (HA) could most effectively remove caseins in porcine milk. We further characterized MEV populations isolated by UC and HA/UC from diverse aspects, including particle methodology via nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), RNA and protein contents, and purity analysis. Importantly, the proliferative and anti-inflammatory effects of MEVs were evaluated in vitro, showing the superiority of MEVs via HA/UC in functionality compared with UC. Our results suggest that HA pretreatment before ultracentrifugation could effectively remove caseins and other protein complexes, leading to MEVs via HA/UC with higher purity and more significant effects in vitro. This study provides valuable insights for the advancement of MEVs isolation techniques across different species and accurate function analysis of MEVs.
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The intestinal ecological environment plays a crucial role in nutrient absorption and overall well-being. In recent years, research has focused on the effects of extracellular vesicles (EVs) in both physiological and pathological conditions of the intestine. The intestine does not only consume EVs from exogenous foods, but also those from other endogenous tissues and cells, and even from the gut microbiota. The alteration of conditions in the intestine and the intestinal microbiota subsequently gives rise to changes in other organs and systems, including the central nervous system (CNS), namely the microbiome-gut-brain axis, which also exhibits a significant involvement of EVs. This review first gives an overview of the generation and isolation techniques of EVs, and then mainly focuses on elucidating the functions of EVs derived from various origins on the intestine and the intestinal microenvironment, as well as the impacts of an altered intestinal microenvironment on other physiological systems. Lastly, we discuss the role of microbial and cellular EVs in the microbiome-gut-brain axis. This review enhances the understanding of the specific roles of EVs in the gut microenvironment and the central nervous system, thereby promoting more effective treatment strategies for certain associated diseases.
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Vesículas Extracelulares , Eje Cerebro-Intestino , Sistema Nervioso Central , Ambiente , AlimentosRESUMEN
Obesity and substantially increased risk of metabolic diseases have become a global epidemic. microRNAs have attracted a great deal of attention as a potential therapeutic target for obesity. MiR-143 has been known to specifically promote adipocyte differentiation by downregulating extracellular signal-regulated kinase 5. Our latest study found that miR-143 knockout is against diet-induced obesity by promoting brown adipose tissue thermogenesis and inhibiting white adipose tissue adipogenesis. Moreover, LPS- or IL-6-induced inhibition of miR-143 expression in brown adipocytes promotes thermogenesis by targeting adenylate cyclase 9. In this review, we will summarize the expression and functions of miR-143 in different tissues, the influence of obesity on miR-143 in various tissues, the important role of adipose-derived miR-143 in the development of obesity, the role of miR-143 in immune cells and thermoregulation and discuss the potential significance and application prospects of miR-143 in obesity management.
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MicroARNs , Obesidad , Humanos , Adipocitos Marrones/metabolismo , Adipogénesis , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Diferenciación Celular , MicroARNs/genética , MicroARNs/metabolismo , Obesidad/tratamiento farmacológico , Termogénesis/genéticaRESUMEN
The hypertrophy and conversion of postnatal muscle fibers largely determine the yield and quality of meat, which is closely related to the economic value of pigs. MicroRNA (miRNA), as a kind of endogenous noncoding RNA molecule, is widely involved in myogenesis of livestock and poultry. The longissimus dorsi tissues of Lantang pigs at 1 and 90 days (LT1D and LT90D) were collected and profiled by miRNA-seq. We found 1871 and 1729 miRNA candidates in LT1D and LT90D samples, and 794 miRNAs were shared. We identified 16 differentially expressed miRNAs between two tested groups and explored the function of miR-493-5p inmyogenesis. The miR-493-5p promoted the proliferation and inhibited the differentiation of myoblasts. Using GO and KEGG analyses of 164 target genes of miR-493-5p, we found that ATP2A2, PPP3CA, KLF15, MED28, and ANKRD17 genes were related to muscle development. RT-qPCR detection showed that the expression level of ANKRD17 was highly expressed in LT1D libraries, and the double luciferase report test preliminarily proved that miR-493-5p and ANKRD17 have a directly targeting relationship. We established miRNA profiles for the longissimus dorsi tissues of 1-day-old and 90-day-old Lantang pigs and found that miR-493-5p was differentially expressed and associated with myogenesis by targeting ANKRD17 gene. Our results should serve as a reference for future studies on pork quality.
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MicroARNs , Porcinos , Animales , MicroARNs/genética , MicroARNs/metabolismo , Mioblastos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Desarrollo de Músculos/genética , Proliferación Celular/genéticaRESUMEN
Background: The prognostic value of coronary artery calcium (CAC) combined with risk factor burdens in middle-aged and elderly patients with symptoms is unclear. Methods: A cohort study comprising 7432 middle-aged and elderly symptomatic patients (aged above 55 years) was conducted between December 2013 and September 2020. All patients had undergone coronary computed tomography angiography, and the Agatston score were used to measure CAC scores. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite outcome of nonfatal myocardial infarction, revascularization (percutaneous coronary intervention or coronary artery bypass graft), stroke, and cardiovascular death. Congestive heart failure, cardiogenic shock, malignant arrhythmia, and all-cause mortality were defined as the secondary outcomes. Results: There are 970 (13%) patients with CAC 0-10, 2331 (31%) patients with CAC 11-100, and 4131 (56%) patients with CAC ≥ 101. The proportion of patients aged 55-65 years, 65-75 years and ≥ 75 years was 40.7%, 38.1% and 21.2%, respectively. The total number of MACCEs over the 3.4 years follow-up period was 478. The percentage of CAC ≥ 101 was higher among the 75-year-old group than the 55-65-year-old group, increasing from 46.5% to 68.2%. With the increase in the CAC score, the proportion of patients aged ≥ 75 years increased from 12.9% to 25.8%, compared to those aged 55-65 years. The number of risk factors gradually increased as the CAC scores increased in the symptomatic patients aged over 55 years and the similar tendencies were observed among the different age subgroups. The proportion of non-obstructive coronary artery disease (CAD) was comparable between the three age groups (53.5% vs 51.9% vs 49.1%), but obstruction CAD increased with age. The incidence of MACCE in the group with CAC ≥ 101 and ≥ 4 risk factors was 1.71 times higher (95% confidence interval (CI) 1.01-2.92; p = 0.044) than the rate in the group with CAC ≥ 101 and 1 risk factor. In the CAC 0-10 group, the incidence of MACCE in patients aged ≥ 75 years was 12.65 times higher (95% CI: 6.74-23.75; p < 0.0001) than that in patients aged 55-65 years. By taking into account the combination of CAC score, age, and risk factor burden, the predictive power of MACCE can be increased (area under the curve (AUC) = 0.614). Conclusions: In symptomatic patients aged 55 or above, a rise in age, CAC scores, and risk factor burden was linked to a considerable risk of future MACCE. In addition, combining CAC scores, age and risk factors can more accurately predict outcomes for middle-aged and elderly patients with symptoms.
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OBJECTIVE: The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. BACKGROUND: The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. METHODS: We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 < CACS ≤ 400, and CACS > 400). RESULTS: 4946 patients [62(55-71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard ß = 0.066, P < 0.001) was positively associated with FAR in patients with chest pain.Compared to ones with FAR-L, FAR-H had an increased risk for MACCEs (adjusted HR 1.371(1.053-1.786) P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001-1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042-1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006-1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250-1.727;p < 0.001) were the independent risk factors for MACCEs. The FAR and CACS significantly improved MACCEs risk stratification, contributing to substantial net reclassification improvement ( NRI 0.122, 95% CI 0.054-0.198, P < 0.001) and integrated discrimination improvement(IDI 0.011, 95% CI 0.006-0.017, P < 0.001). CONCLUSION: FAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs.
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Enfermedad de la Arteria Coronaria , Calcificación Vascular , Femenino , Humanos , Masculino , Dolor en el Pecho , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/complicaciones , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagen , Persona de Mediana Edad , AncianoRESUMEN
OBJECTIVE: To investigate the possible association between AT1R gene polymorphisms and major adverse cardiovascular and cerebrovascular events (MACCEs) in hypertension patients combined with or without coronary artery disease (CAD) in Xinjiang. METHODS: 374 CAD patients and 341 non-CAD individuals were enrolled as study participants and all of them have a hypertension diagnosis. AT1R gene polymorphisms were genotyped by SNPscan™ typing assays. During the follow-up in the clinic or by telephone interview, MACCEs were recorded. Kaplan-Meier curves and Cox survival analyses were used to explore the association between AT1R gene polymorphisms and the occurrence of MACCEs. RESULTS: AT1R gene rs389566 was associated with MACCEs. The TT genotype of the AT1R gene rs389566 had a significantly higher probability of MACCEs than the AA + AT genotype (75.2% vs. 24.8%, P = 0.033). Older age (OR = 1.028, 95% CI: 1.009-1.0047, P = 0.003) and TT genotype of rs389566 (OR = 1.770, 95% CI: 1.148-2.729, P = 0.01) were risk factors of MACCEs. AT1R gene rs389566 TT genotype may be a predisposing factor for the occurrence of MACCEs in hypertensive patients. CONCLUSION: We should also pay more attention to the prevent of MACCEs in hypertension patients combined with CAD. Especially those elderly hypertensive patients carrying AT1R rs389566 TT genotype requires avoidance of unhealthy lifestyle, better management of blood pressure control and reduce the occurrence of MACCEs.
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Enfermedad de la Arteria Coronaria , Hipertensión , Receptor de Angiotensina Tipo 1 , Anciano , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/genética , Genotipo , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/genética , Polimorfismo Genético , Receptor de Angiotensina Tipo 1/genética , Factores de RiesgoRESUMEN
BACKGROUND: The early development of intestinal microbiota plays a fundamental role in host health and development. To investigate the difference in the intestinal microbial composition between Lantang and Landrace newborn piglets, we amplified and sequenced the V3-V4 region of 16 S rRNA gene in jejunal microbiota of Lantang and landrace newborn. RESULTS: The findings revealed that the dominant phyla in the jejunum of Lantang piglets were Firmicutes, Actinobacteria and Bacteroidetes, while the dominant phyla of Landrace is Proteobacteria and Fusobacteria. Specifically, Corynebacterium_1, Lactobacillus, Rothia, Granulicatella, Corynebacteriales_unclassified, Corynebacterium, Globicatella and Actinomycetales_unclassified were found to be the dominant genera of Lantang group, while Clostridium_sensu_stricto_1, Escherichia-Shigella, Actinobacillus and Bifidobacterium were the dominant genera of Landrace. Based on the functional prediction of bacteria, we found that bacterial communities from Lantang samples had a significantly greater abundance pathways of fatty acid synthesis, protein synthesis, DNA replication, recombination, repair and material transport across membranes, while the carrier protein of pathogenic bacteria was more abundant in Landrace samples. CONCLUSIONS: Overall, there was a tremendous difference in the early intestinal flora composition between Landang and Landrace piglets, which was related to the breed characteristics and may be one of the reasons affecting the growth characteristics. However, more further extensive studies should be included to reveal the underlying relationship between early intestinal flora composition in different breeds and pig growth characteristics.
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Microbioma Gastrointestinal , Animales , Porcinos , Animales Recién Nacidos , Fitomejoramiento , Bacterias/genética , Yeyuno/microbiología , ARN Ribosómico 16S/genéticaRESUMEN
OBJECTIVE: To clarify the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on the clinical outcomes of patients with coronary heart disease (CHD) complicated with reduced ejection fraction heart failure (HFrEF) through meta-analysis. METHODS: Three major literature databases - PubMed, Web of Science, and Cochrane - were searched by search terms and the literature retrieval time was publications dating from January 2007 to December 2021. To search for observational studies and randomized controlled trials (RCT) comparing the efficacy of PCI and CABG in patients with CHD and HFrEF, the abstract or full text of the literature was read and the final included literature was determined, according to inclusion and exclusion criteria. The quality of the included literature was evaluated using the Ottawa scale and data extraction was further completed. Data analysis was made using RevMan5.4 and R4.1 software; relevant forest plots and funnel plots were made, according to the extracted data. Egger's test was used to evaluate whether the data had publication bias. Outcomes were the major adverse cardiovascular events (MACE). RESULTS: A total of 10 studies were included and 11,032 subjects were included, made up of 5,521 cases of PCI and 5,511 cases of CABG. The results showed no significant difference between the two groups in cardiac mortality (CM) (RR=1.13, 95% CI 0.98-1.30, P = 0.10) and in overall all-cause mortality (ACM) (RR=1.12, 95% CI 0.92-1.37, P = 0.25). In the subgroup analysis of ACM, in the subgroups with left ventricular ejection fraction (LVEF) less than 35% and exceeding 35% and less than 50% (RR=1.12, 95% CI 0.92-1.37, P = 0.25) between the two groups, there was no statistical difference. However, among other MACE, compared with the PCI group, the CABG group had a lower risk of MACE (RR=1.58, 95%CI 1.49-1.70, P < 0.00001), myocardial infarction (MI) (RR=1.99, 95% CI 1.02-3.88, P = 0.04), heart failure (HF) (RR=1.29, 95% CI 1.17-1.43, P < 0.00001) and revascularization (RR=2.74, 95% CI 1.93-3.90, P < 0.00001). Finally in the CABG group, the risk of stroke or transient ischemic attack (TIA) was higher (RR=0.71, 95% CI 0.58-0.86, P = 0.0006) than the PCI group. CONCLUSIONS: The mortality rates of PCI and CABG were similar in patients with CHD complicated with HFrEF. Compared with PCI, CABG had a lower incidence of MACE, MI, HF, and revascularization, and a higher incidence of stroke or TIA.
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Enfermedad Coronaria , Insuficiencia Cardíaca , Ataque Isquémico Transitorio , Infarto del Miocardio , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Humanos , Puente de Arteria Coronaria , Volumen Sistólico , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Exosomes are key mediators of intercellular communication. They are secreted by most cells and contain a cargo of protein-coding genes, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), which modulate recipient cell behavior. Herein, we collected blood samples from Holstein cows at days 30 (mid-lactation) and 250 (dry period) of pregnancy. Prolactin, follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone levels showed an obvious increase during D250. We then extracted exosomes from bovine blood samples and found that their sizes generally ranged from 100 to 200 nm. Further, Western blotting validated that they contained CD9, CD63, and TSG101, but not calnexin. Blood-derived exosomes significantly promoted the proliferation of mammary epithelial cells, particularly from D250. This change was accompanied by increased expression levels of proliferation marker proteins PCNA, cyclin D, and cyclin E, as detected by EdU assay, cell counting kit-8 assay, and flow cytometric cell cycle analysis. Moreover, we treated mammary epithelial cells with blood-derived exosomes that were isolated from the D30 and D250 periods. And RNA-seq of two groups of cells led to the identification of 839 differentially expressed genes that were significantly enriched in KEGG signaling pathways associated with apoptosis, cell cycle and proliferation. In bovine blood-derived exosomes, we found 12,747 protein-coding genes, 31,181 lncRNAs, 9374 transcripts of uncertain coding potential (TUCP) candidates, and 460 circRNAs, and 32 protein-coding genes, 806 lncRNAs, 515 TUCP candidates, and 45 circRNAs that were differentially expressed between the D30 and D250 groups. We selected six highly expressed and four differentially expressed circRNAs to verify their head-to-tail splicing using PCR and Sanger sequencing. To summarize, our findings improve our understanding of the key roles of blood-derived exosomes and the characterization of exosomal circRNAs in mammary gland development.
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Exosomas , MicroARNs , ARN Largo no Codificante , Embarazo , Femenino , Bovinos , Animales , ARN Circular/genética , ARN Circular/metabolismo , Exosomas/metabolismo , ARN Largo no Codificante/metabolismo , Lactancia , Transducción de Señal , MicroARNs/genéticaRESUMEN
Skeletal muscle-fat interaction is essential for maintaining organismal energy homeostasis and managing obesity by secreting cytokines and exosomes, but the role of the latter as a new mediator in inter-tissue communication remains unclear. Recently, we discovered that miR-146a-5p was mainly enriched in skeletal muscle-derived exosomes (SKM-Exos), 50-fold higher than in fat exosomes. Here, we investigated the role of skeletal muscle-derived exosomes regulating lipid metabolism in adipose tissue by delivering miR-146a-5p. The results showed that skeletal muscle cell-derived exosomes significantly inhibited the differentiation of preadipocytes and their adipogenesis. When the skeletal muscle-derived exosomes co-treated adipocytes with miR-146a-5p inhibitor, this inhibition was reversed. Additionally, skeletal muscle-specific knockout miR-146a-5p (mKO) mice significantly increased body weight gain and decreased oxidative metabolism. On the other hand, the internalization of this miRNA into the mKO mice by injecting skeletal muscle-derived exosomes from the Flox mice (Flox-Exos) resulted in significant phenotypic reversion, including down-regulation of genes and proteins involved in adipogenesis. Mechanistically, miR-146a-5p has also been demonstrated to function as a negative regulator of peroxisome proliferator-activated receptor γ (PPARγ) signaling by directly targeting growth and differentiation factor 5 (GDF5) gene to mediate adipogenesis and fatty acid absorption. Taken together, these data provide new insights into the role of miR-146a-5p as a novel myokine involved in the regulation of adipogenesis and obesity via mediating the skeletal muscle-fat signaling axis, which may serve as a target for the development of therapies against metabolic diseases, such as obesity.
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Exosomas , MicroARNs , Ratones , Animales , PPAR gamma/metabolismo , Adipogénesis/genética , Tejido Adiposo/metabolismo , MicroARNs/genética , Músculo Esquelético/metabolismo , Obesidad/metabolismo , Exosomas/metabolismo , Factor 5 de Diferenciación de Crecimiento/metabolismoRESUMEN
Exposure to ultraviolet light can cause oxidative damage and accelerate skin aging and is one of the main causes of skin aging. Peach gum polysaccharide (PG) is a natural edible plant component that has many biological activities, such as regulating blood glucose and blood lipids and improving colitis, as well as antioxidant and anticancer properties. However, there are few reports on the antiphotoaging effect of peach gum polysaccharide. Therefore, in this paper, we study the basic composition of the raw material peach gum polysaccharide and its ability to improve UVB-induced skin photoaging damage in vivo and in vitro. The results show that peach gum polysaccharide is mainly composed of mannose, glucuronic acid, galactose, xylose, and arabinose, and its molecular weight (Mw) is 4.10 × 106 g/mol. The results of the in vitro cell experiments show that PG could significantly alleviate UVB-induced apoptosis of human skin keratinocytes, promote cell growth repair, reduce the expression of intracellular oxidative factors and matrix metal collagenase, and improve the extent of oxidative stress repair. Moreover, the results from the in vivo animal experiments showed that PG could not only effectively improve the phenotype of UVB-induced photoaged skin in model mice but also significantly improve their oxidative stress status, regulate the contents of ROS and the levels of SOD and CAT, and repair the oxidative skin damage induced by UVB in vivo. In addition, PG improved UVB-induced photoaging-mediated collagen degradation in mice by inhibiting the secretion of matrix metalloproteinases. The above results indicate that peach gum polysaccharide has the ability to repair UVB-induced photoaging and may be used as a potential drug and antioxidant functional food to resist photoaging in the future.
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Prunus persica , Envejecimiento de la Piel , Ratones , Humanos , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Prunus persica/metabolismo , Piel/metabolismo , Estrés Oxidativo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Rayos Ultravioleta/efectos adversos , FibroblastosRESUMEN
BACKGROUND: Long-term artificial selection for growth rate and lean meat rate has eventually led to meat quality deterioration. Muscle fiber type is a key factor that markedly affects meat quality. circRNAs have been reported to participate in diverse biological activities, including myofiber growth and development; thus, we herein compared porcine circRNA transcriptome between oxidative and glycolytic muscle tissues. RESULTS: Longissimus thoracis muscle tissues were obtained from Lantang and Landrace pigs at birth (LT1D and LW1D, respectively) and 90 postnatal days (LT90D and LW90D, respectively). Hematoxylin and eosin staining and quantitative real-time PCR revealed that all structural traits of the muscle showed large variations between different breeds and growth stages. In total, 329 known miRNAs and 42,081 transcript candidates were identified; 6,962 differentially expressed transcripts were found to play a key role in myogenesis by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In addition, 3,352 circRNAs were identified using five predicting algorithms, and 104 circRNA candidates were differentially expressed. Integrated analysis of differentially expressed miRNAs, mRNAs, and circRNAs led to the identification of 777, 855, and 22 convincing ceRNA interactions in LT1D vs. LT90D, LW1D vs. LW90D, and LT90D vs. LW90D, respectively. Finally, we identified a circRNA candidate circKANSL1L, which showed high homology between mice and pigs, and it was found to inhibit the proliferation of C2C12 cells but promote their differentiation. CONCLUSIONS: We identified genome-wide circRNAs in 0- and 90-day-old Lantang and Landrace pigs by RNA-seq and found that circRNAs were abundant, differentially expressed, and associated with myogenesis. Our results should serve as a reference for future studies on pork quality.
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MicroARNs , ARN Circular , Animales , Perfilación de la Expresión Génica/métodos , Ratones , MicroARNs/genética , Desarrollo de Músculos/genética , ARN Circular/genética , Porcinos/genética , TranscriptomaRESUMEN
Accumulating evidence has demonstrated that diet-derived gut microbiota participates in the regulation of host metabolism and becomes the foundation for precision-based nutritional interventions and the biomarker for potential individual dietary recommendations. However, the specific mechanism of the gut microbiota-host crosstalk remains unclear. Recent studies have identified that noncoding RNAs, as important elements in the regulation of the initiation and termination of gene expression, mediate microbiota-host communication. Besides, the cross-kingdom regulation of non-host derived microRNAs also influence microbiota-host crosstalk via diet motivation. Hence, understanding the relationship between gut microbiota, miRNAs, and host metabolism is indispensable to revealing individual differences in dietary motivation and providing targeted recommendations and strategies. In this review, we first present an overview of the interaction between diet, host genetics, and gut microbiota and collected some latest research associated with microRNAs modulated gut microbiota and intestinal homeostasis. Then, specifically described the possible molecular mechanisms of microRNAs in sensing and regulating gut microbiota-host crosstalk. Lastly, summarized the prospect of microRNAs as biomarkers in disease diagnosis, and the disadvantages of microRNAs in regulating gut microbiota-host crosstalk. We speculated that microRNAs could become potential novel circulating biomarkers for personalized dietary strategies to achieve precise nutrition in future clinical research implications.
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BACKGROUND: Several studies have reported that NFKB1 gene rs28362491 polymorphism was associated with susceptibility to coronary heart disease in populations of different genetic backgrounds. To date, there have been no studies on the association between NFKB1 gene rs28362491 polymorphism and the occurrence of major adverse cardiac and cerebrovascular event (MACCE). The present study was to explore the relationship between NFKB1 gene rs28362491 polymorphism and MACCEs to investigate whether identifying NFKB1 gene polymorphism is beneficial to evaluating MACCE risks and patients' prognoses. METHODS: We recruited 257 high-risk of cardiovascular disease patients with chest pain or precordial discomfort. The SNPscan™ were used to analyze the NFKB1 gene rs28362491 polymorphism. All patients were followed up in the clinic or by telephone interview for MACCEs. RESULTS: During the followed-up time (mean: 30.1 months) 49 patients had MACCEs (19.1%). Patients with the different genotypes of NFKB1 rs28362491 had different incidence rate of MACCE. The incidence of MACCE in patients carried II, ID and DD genotype was 16.5%, 15.9%, 32.6%, respectively. Log-rank analysis showed that the survival rate in patients with NFKB1 rs28362491 DD genotype was much lower than that in II or ID genotype carriers (P = 0.034). After excluding the influence of traditional risk factors of MACCEs, Cox regression showed that the DD genotype carriers had 2.294-fold relative risk of MACCEs comparing with patients carried II or ID genotype. CONCLUSION: The NFKB1 gene rs28362491 mutant was an independent predictor of worse long-term prognosis for MACCEs. Therefore, identifying NFKB1 gene rs28362491 mutant may be used as a good way for guiding the standardized management of patients with high-risk of cardiovascular diseases.
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Enfermedades Cardiovasculares , Predisposición Genética a la Enfermedad , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Estudios de Casos y Controles , Genotipo , Humanos , Mutación , Subunidad p50 de NF-kappa B/genéticaRESUMEN
BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that the MALAT1 gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of the MALAT1 polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between the MALAT1 rs3200401 polymorphism and MACCEs. METHOD: We enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect the MALAT1 rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan-Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation between MALAT1 gene polymorphisms and the occurrence of MACCEs. RESULTS: Among the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%, P = 0.047, MI patients 20.7% vs. 14.1%, P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%, P = 0.013, MI patients 39.5% vs. 25.8%, P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%, P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%, P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan-Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015, P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060-2.277, P = 0.024). CONCLUSIONS: The MALAT1 rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that the MALAT1 gene may become a biomarker for poor prognosis in MI patients.
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Infarto del Miocardio , ARN Largo no Codificante , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple , Pronóstico , ARN Largo no Codificante/genéticaRESUMEN
BACKGROUND: To explore possible associations between glucose transporter 4 (GLUT4) genetic polymorphisms in the patients with coronary heart disease (CHD) in Han and Uygur Chinese populations in Xinjiang, China. METHODS: Two GLUT4 polymorphisms (rs5418 and rs5435) were genotyped in 1262 Han (628 CHD patients and 634 healthy controls) and 896 Uyghur (397 CHD patients and 499 healthy controls) Chinese populations. RESULTS: In the Han Chinese population, there were no significant differences in allelic or genotypic distribution of rs5418 and rs5435 between the CHD and control groups (all P > 0.05). However, in the Uygur population, there were significant differences in genotype and allele distributions for rs5418 between CHD and the control group (all P < 0.05). Binary Logistic regression analysis showed that carriers with the rs5418 A allele had a higher risk of CHD compared to carriers of the rs5418 G allele (OR = 1.33, 95% CI: 1.069-1.649, P = 0.01), after adjustment for gender, age, drinking and smoking behavior, hypertension and diabetes. Furthermore, haploid association analysis of the two SNP loci of the GLUT4 gene showed that the AC haplotype was associated with CHD in the Uygur population (P = 0.001598; OR = 1.36, 95% CI = 1.1228-1.6406). CONCLUSIONS: rs5418 GLUT4 gene variants are associated with CHD in the Uygur Chinese population.