RESUMO
Naoxintong capsule (NXT) is a clinical drug for the treatment of cardiovascular diseases, but its pharmacological mechanism against hypertension remains unclear. Data concerning the compounds and targets of NXT were obtained from the TCMSP and DrugBank, whereas data concerning hypertension-related genes were obtained from DisGeNET. The network was analyzed and established by STRING and Cytoscape, and function enrichment was analyzed by GO and KEGG analysis. Molecular docking was performed to analyze the interaction between ingredients and targets, cellular activity was evaluated by MTT assay, and RT-qPCR and western blot were used to evaluate the expressions of related genes. The results showed that 146 active therapeutic components can target hypertension-related genes, and we found that core genes were mainly involved in the metabolism of lipids, lipopolysaccharides, the inflammatory signaling pathway, and the oxidative stress pathway. In addition, there was high affinity between the components of NXT and targets of hypertension, where the former can increase cell viability and reduce the expressions of NOX4, MCP-1, BAX, TNF-α and IL-1ß. Moreover, NXT inhibited the expressions of IL-6 and Fis1, as well as increased the expression of MCL-1. These results revealed the active compounds, hypertension targets, signaling pathways, and molecular mechanisms of NXT for treating hypertension, offering references for the clinical application of NXT and the treatment of hypertension.
Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Hipertensão , Humanos , Simulação de Acoplamento Molecular , Hipertensão/tratamento farmacológico , Fator de Necrose Tumoral alfa , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
BACKGROUND: Sarcopenia is an age-related clinical syndrome characterized by loss of muscle mass and reduced muscle function. Diseases that contribute to sarcopenia include type 2 diabetes mellitus (T2DM), chronic obstructive pulmonary disease (COPD), heart failure, chronic kidney disease, and cancer and others. Fung FY et al. (BMC Geriatrics. 2019;19(1):122) conducted a single-center study aimed to determine the prevalence of sarcopenia among older patients with T2DM and to identify factors which mitigate sarcopenia. Their study entitled "Prevalence of and factors associated with sarcopenia among multi-ethnic ambulatory older Asians with type 2 diabetes mellitus in a primary care setting" suggested that the prevalence of sarcopenia in older patients with T2DM was 27.4%, and that Chinese ethnicity was associated with a greater risk of sarcopenia in the study population. DISCUSSION: Deficiency in scientific research and analysis of other diseases associated with sarcopenia such as COPD, may contribute to misestimation of the prevalence of sarcopenia in older patients with T2DM. We are concerned that the conclusions of this single-center study with a small study population might be unreliable. The prevalence of sarcopenia in older patients with T2DM in a single-center study with a small sample size may be misestimated due to the lack of strict exclusion criteria and detailed analysis of other diseases that contribute to sarcopenia. In addition, it is inappropriate to draw the conclusion that Chinese ethnic group was associated with a greater risk of sarcopenia among the study population.
RESUMO
Circular RNAs (circRNAs) are single-strand covalently closed circular noncoding RNAs that are endogenous transcripts generated from linear precursor mRNA through a backsplicing mechanism. With the development of high-throughput sequencing technology, a number of circRNAs have been identified and proved to play key roles in various pathophysiological processes, such as metabolic diseases, cancers, and cardiovascular diseases. An increasing number of studies have shown that circRNAs are widely expressed in cardiac tissues and play important roles in the development of multiple cardiovascular diseases. Here, we review the current understanding of circRNA biogenesis and functions and the roles of circRNAs in cardiovascular diseases. We also highlight the molecular mechanisms underlying the role of circRNAs in the pathogenesis of cardiovascular diseases. A better understanding of the biological function of circRNAs in cardiovascular diseases will be helpful for the development of effective biomarkers for the diagnosis and treatment of these diseases.
Assuntos
Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , RNA Circular/metabolismo , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/patologia , Sistema Cardiovascular/fisiopatologia , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Splicing de RNA , RNA Circular/sangue , RNA Circular/genética , Transdução de SinaisRESUMO
The use of circulating microRNAs as biomarkers opens up new opportunities for the diagnosis of cardiovascular diseases because of their specific expression profiles. The aim of the present study was to identify circulating microRNAs in human plasma as potential biomarkers of heart failure and related diseases. We used real-time quantitative PCR to screen microRNA in plasma samples from 62 normal controls and 62 heart failure samples. We found that circulating miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 expressed differently between healthy controls and heart failure patients. Plasma levels of miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 were unaffected by hemolysis. Correlation analysis showed any two of these miRNAs possess a strong correlation, indicating a possibility of combined analysis. MiR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 could be combined in two or three or more combinations. The results suggest that miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 may be a new diagnostic biomarker for heart failure and related diseases.
Assuntos
Perfilação da Expressão Gênica/métodos , Insuficiência Cardíaca/genética , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/genética , China , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
microRNAs are a type of evolutionarily conserved small non-coding RNA with a length of 18-25 nucleotides. In recent years, increasing studies have shown that the content of specific miRNAs in the blood changes significantly during the occurrence and development of major diseases such as cardiovascular disease and cancer. Therefore, miRNAs may serve as important new biomarkers that can be used for disease diagnosis in the future. Here, we improved the polyethylene glycol layer on the surface of a traditional silicon sphere to specifically capture miRNAs by means of a full-function microplate detector, at 100 microliters. The detection limit for specific miRNAs per liter of plasma can reach 1 fM, and simultaneous detection of 96 samples can be achieved. Compared with the traditional real-time PCR technology, our detection eliminates the complex steps of miRNA extraction, reverse transcription, amplification, etc. and avoids more human error in the detection process. Using the full-featured microwell detector, we can rapidly detect specific miRNAs in plasma, which can be used in the diagnosis of cardiovascular diseases in the future.
Assuntos
Biomarcadores Tumorais/sangue , Doenças Cardiovasculares/sangue , MicroRNA Circulante/sangue , Neoplasias/sangue , RNA Neoplásico/sangue , Adulto , Humanos , Limite de Detecção , MasculinoRESUMO
Alginate oligosaccharide (AOS) has recently demonstrated the ability to protect against acute doxorubicin cardiotoxicity and neurodegenerative disorders by inhibiting oxidative stress and endoplasmic reticulum (ER) stress-mediated apoptosis, which are both involved in myocardial ischemia/reperfusion (I/R) injury. In the present study, we investigated whether pretreatment with AOS protects against myocardial I/R injury in mice and explored potential cardioprotective mechanisms. AOS pretreatment significantly decreased the infarct size, reduced the cardiac troponin-I concentration, and ameliorated the cardiac dysfunction. Accompanied with the reduced cardiac injury, AOS pretreatment clearly decreased I/R-induced myocardial apoptosis. With regard to mechanism, AOS pretreatment markedly attenuated nitrative/oxidative stress, as evidenced by decreases in 3-nitrotyrosine content and superoxide generation, and downregulated inducible nitric oxide synthase, NADPH oxidase2, and 4-hydroxynonenal. Moreover, AOS pretreatment decreased myocardial apoptosis by inhibiting the ER stress-mediated apoptosis pathway, which is reflected by the downregulation of C/EBP homologous protein, glucose-regulated protein 78, caspase-12, and Bcl-2-associated X protein, and by the upregulation of the anti-apoptotic protein B-cell lymphoma-2. Collectively, these findings demonstrate that AOS renders the heart resistant to I/R injury, at least in part, by inhibiting nitrative/oxidative stress and ER stress-mediated apoptosis.