Uncovering the mechanism of Naoxintong capsule against hypertension based on network analysis and in vitro experiments.

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.

Microplastics in 48 wastewater treatment plants reveal regional differences in physical characteristics and shape-dependent removal in the transition zone between North and South China.

This study investigated the physical characteristics and removal efficiency of microplastics in wastewater from regions with different climatic conditions and economic development levels. Microplastics with different shapes and sizes were analyzed from the influent and effluent of 48 wastewater treatment plants in three regions of Shaanxi Province (China). Results indicated that the abundance of microplastics in the influent samples was higher in the region with less regional water resources. However, the per capita microplastics emissions was higher in the region with higher economic development level. There were less fibers and more foams and beads in the more developed region. The removal efficiency of microplastics was related to their shape and size. Particularly, the removal efficiency showed a significant negative correlation with the percentage of foams, while it had a significant positive relationship with the proportions of films and fibers. The highest removal efficiency was obtained when the size of microplastics was ranged from 0.5 to 1.0 mm. This study suggests, compared to improving the removal efficiency of microplastics, that reducing the input at source is a more scientific and promising method.

Isolevuglandins Scavenger Ameliorates Myocardial Ischemic Injury by Suppressing Oxidative Stress, Apoptosis, and Inflammation.

Augmented levels of reactive isolevuglandins (IsoLGs) are responsible for cardiovascular diseases. The role of IsoLGs in myocardial infarction (MI) remains elusive. Here we explored the effect of IsoLGs scavenger 2-hydroxybenzylamine (2-HOBA) in post-infarction cardiac repair. We observed that infarcted cardiac tissues expressed high IsoLGs in mice. Following MI injury, 2-HOBA treated mice displayed decreased infarction area and improved heart function compared with the saline-treated group. Moreover, 2-HOBA effectively attenuated MI-induced cardiac remodeling, oxidative stress, apoptosis, and inflammation. 4-hydroxybenzylamine (4-HOBA), a less reactive isomer of 2-HOBA, barely antagonized the MI-induced injury. These findings suggest that IsoLGs elimination may be helpful in MI therapy.

Bacterial abundance and community structure in response to nutrients and photodegraded terrestrial humic acids in a eutrophic lake.

The exposure of humic substances to solar radiation can alter their concentration and composition and subsequently influences their bioavailability in aquatic food webs. With eutrophication increasingly prominent in lakes, nutrients, such as inorganic N and P, are a prerequisite for heterotrophic bacteria that use organic matter. Here photodegradation of terrestrial humic acids and nutrient addition were performed to investigate the response of bacterial abundance and community structure to photodegraded humic acids and increased nutrient concentrations in a eutrophic lake. Results showed that the decreasing level of absorption coefficient at 460 nm in the treatment irradiated with 40 W UV lamps was more remarkable than that of the treatment irradiated with 20 W UV lamps and the control. This reduced coefficient corresponds to the greatest decrease in humic acid concentration in the 40 W group. Bacteria showed high abundance after incubation with humic acids which underwent strong irradiation intensity. An increased nutrient concentration significantly affected bacterial abundance. The dominant bacteria were Aquabacterium for the irradiated group, Aquabacterium and Limnobacter for the 20 W group and Flavobacterium and Limnobacter for the 40 W group. Armatimonadetes-gp4 and Sediminibacterium showed evident response to high nutrient concentration. Our results showed that the exposure of terrestrial humic acids to UV light and the increasing concentration of nutrients have obviously changed bacterial community.

Revisiting: "prevalence of and factors associated with sarcopenia among multi-ethnic ambulatory older Asians with type 2 diabetes mellitus in a primary care setting".

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.

Role of Circular RNAs in the Pathogenesis of Cardiovascular Disease.

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.

Circular RNA-Expression Profiling Reveals a Potential Role of Hsa_circ_0097435 in Heart Failure via Sponging Multiple MicroRNAs.

Circular RNAs represent a new type of non-coding RNA molecules that influence the occurrence and development of various human diseases by sponging microRNAs, although their roles in heart failure have not been clarified. In this study, peripheral blood samples from 5 patients with heart failure and 4 healthy volunteers were analyzed by next-generation sequencing (NGS) to screen for differentially expressed Circular RNAs. Fifty-six differentially expressed Circular RNAs were identified, of which 29 were up-regulated and 27 were down-regulated. Dysregulated expression of 6 Circular RNAs was verified by quantitative polymerase chain reaction (PCR) analysis, and hsa_circ_0097435 expression was confirmed to be significantly up-regulated in 40 patients with heart failure. Further study with extracted exosomes showed that hsa_circ_0097435 expression was significantly higher in patients with heart failure. In cardiomyocytes, hsa_circ_0097435 was up-regulated after doxorubicin treatment, promoting cardiomyocyte apoptosis. Hsa_circ_0097435 overexpression promoted cardiomyocyte apoptosis, and silencing hsa_circ_0097435 inhibited apoptosis. Moreover, RNA-pulldown experiments and AGO2-immunoprecipitation experiments revealed that hsa_circ_0097435 potentially served a role in heart failure by sponging multiple microRNAs. Collectively, these results suggest that hsa_circ_0097435 can be used as a biological blood marker and revealed a new pathway involved in regulating myocardial cell injury. Our findings may provide a rational basis for developing new treatments for heart failure.

Combined detection of miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 for screening of early heart failure diseases.

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.

The role of mitochondrial fusion and fission in the process of cardiac oxidative stress.

Mitochondria are the energy suppliers in the cell and undergo constant fusion and fission to meet metabolic demand during the cell life cycle. Well-balanced mitochondrial dynamics are extremely important and necessary for cell survival as well as for tissue homeostasis. Cardiomyocytes contain large numbers of mitochondria to satisfy the high energy demand. It has been established that deregulated processes of mitochondrial dynamics play a major role in myocardial cell death. Currently, cardiac mitochondrial cell death pathways attract great attention in the cell biology and regenerative medicine fields. Importantly, mitochondrial dynamics are tightly linked to oxidative stress-induced cardiac damage. This review summarizes molecular mechanisms of mitochondrial fusion and fission processes and their potential roles in myocardial cell death triggered by oxidative stress. Advances in understanding the effect of both normal and abnormal mitochondrial dynamics on heart protection will lead to significant improvement of therapeutic discoveries.

Large-scale rapid detection of circulating microRNAs in plasma for diagnosis and screening of specific diseases.

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.

KCNQ1OT1, HIF1A-AS2 and APOA1-AS are promising novel biomarkers for diagnosis of coronary artery disease.

This study aimed to evaluate the potential of long noncoding RNAs (lncRNAs) as biomarkers for coronary artery disease (CAD). We measured the levels of three atherosclerosis- or cardiac-related lncRNAs in peripheral blood monocyte cells (PBMCs) from 20 CAD patients and 20 non-CAD control participants using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) methods. We found that the levels of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) and apolipoprotein A-1 antisense RNA (APOA1-AS) were significantly increased in CAD patients (KCNQ1OT1 increased by 2.38-fold, P = 0.00042; HIF1A-AS2 increased by 2.00-fold, P = 0.0001; APOA1-AS increased by 4.52-fold, P = 0.000048). The area under the ROC curve was 0.865 for KCNQ1OT1, 0.852 for HIF1A-AS2, and 0.967 for APOA1-AS. Furthermore, the combination of lncRNAs resulted in a much higher AUC value of 0.990 for the prediction of CAD. Spearman's correlation analysis showed that APOA1-AS was positively correlated with NT-proBNP, CKMB, MYO and HsTnT, whereas HIF1A-AS2 was correlated with NT-proBNP and HsTnT. Hence, the elevation of KCNQ1OT1, HIF1A-AS2 and APOA1-AS predicts CAD and these molecules may be considered as novel biomarkers of CAD.

Peripheral T cell receptor beta immune repertoire is promptly reconstituted after acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is characterized by an inflammatory process in which T cell plays a key role. However, the profile of immune microenvironment in AMI is still uncertain. High-throughput sequencing of T cell receptor (TCR) provides deep insight into monitoring the immune microenvironment. METHODS: 30 patients with AMI were enrolled and 30 healthy individuals were recruited as controls. Flow cytometer were used to analyze the distribution of αß T cells and their CD69 expression from peripheral leukomonocytes. TCRß repertoire library was amplified by two-round multiplex PCR and detected by next-generation sequencing (NGS). RESULTS: The percentage of αß T cells in AMI patients were significantly restricted than those in healthy controls, while the highly activated αß T cells along with distinguishing usage of variable (V), diversity (D) and joining (J) gene segments were also found in AMI patients. In addition, AMI induced a significantly restricted CDR3 amino acid (AA) diversity and remarkably reconstituted TCR immune repertoires. Finally, we identified several AMI-associated tendency of CDR3 AAs expression after AMI. CONCLUSIONS: Our work suggests that the aberrant αß T cells distribution and activation may associated with the pathogenesis of AMI and demonstrates a reconstitution of TCRß immune repertoire after AMI.

Circulating miR-22-5p and miR-122-5p are promising novel biomarkers for diagnosis of acute myocardial infarction.

BACKGROUND/AIMS: This study sought to evaluate the potential of circulating microRNAs (miRNAs) as novel indicators for acute myocardial infarction (AMI). METHODS: Plasma samples were collected from each participant, and total RNA was extracted. Quantitative real-time polymerase chain reaction were used to investigate the expression of circulating miRNAs. We measured circulating levels of six individual miRNAs, which are known to be relevant to AMI, in the plasma samples from 66 AMI patients and 70 non-AMI healthy comparisons. RESULTS: Five small RNAs were specifically expressed in AMI patients, plasma miR-122-5p levels is significantly elevated (p < 0.0001) in AMI patients, while plasma miR-22-5p ( p < 0.05) levels were significantly decreased. In addition, significant correlations between miR-22-5p and miR-122-5p ( R = 0.773), miR-122-5p and creatine kinase isoenzyme (CK-MB; R = 0.6296) were detected. Further, receiver operating characteristic (ROC) analysis indicated that miR-22-5p showed considerable diagnostic efficiency for predicting AMI (area under the curve [AUC] = 0.975). Combining miR-22-5p and miR-122-5p in a panel increased the sensitivity (98.6%) of distinguishing between patients with AMI and healthy comparisons. CONCLUSION: Circulating miR-22-5p and miR-122-5p could be considered promising novel diagnostic biomarkers for AMI.

Characterization of the complete mitochondrial genome of the lung fluke, Paragonimus heterotremus.

In this study, the complete mitochondrial genome of human lung fluke, Paragonimus heterotremus, was recovered through Illumina sequencing data. This complete mitochondrial genome of P. heterotremus is 13,927 bp in length and has a base composition of A (16.6%), T (41.8%), C (13.%), G (28.4%), demonstrating an obvious bias of high AT content (58.4%). The mitochondrial genome contains a typically conserved structure, encoding 12 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (12S rRNA and 16S rRNA) and a control region (D-loop region). All PCGs were located on the H-strand. ND4 gene and ND4L gene were overlapped by 39 bp. The nucleotide sequence of 12 PCGs of P. heterotremus and other 10 parasite species were used for phylogenetic analysis. The result indicated P. heterotremus a relative close relationship with species Paragonimus westermani (AF219379.2).

Alginate oligosaccharide alleviates myocardial reperfusion injury by inhibiting nitrative and oxidative stress and endoplasmic reticulum stress-mediated apoptosis.

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.