Gut microbiota might mediate the benefits of high-fiber/acetate diet to cardiac hypertrophy mice

Continuously prolonged cardiac hypertrophy results in maladaptive myocardial remodeling, which affects cardiac function and can eventually lead to heart failure. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, have been reported to be associated with cardiovascular diseases (CVD). Gut microbiota may mediate between dietary fiber and SCFA effects on cardiac hypertrophy. The mice model of isoproterenol (ISO)-induced cardiac hypertrophy was constructed and verified for physiological, functional, and fibrotic alterations in this study. Both high-fiber and acetate diet improved physiological indexes, ameliorated cardiac functions, and relieved fibrotic alterations in model mice hearts; collectively, cardiac hypertrophy in mice receiving both high-fiber and acetate diet improved. Following 16s rDNA sequencing and integrative bioinformatics, analyses indicated that both high-fiber and acetate diet caused alterations in mice gut microbiota compared with the ISO group, including OTU composition and abundance. In conclusion, high-fiber and acetate diet improve the physiological status, cardiac functions, and fibrotic alterations in ISO-induced hypertrophic mice. Besides, considering the alterations in mice gut microbiota in response to single ISO, both high-fiber and acetate diet treatment, gut microbiota might mediate the favorable benefits of both high-fiber and acetate diet on cardiac hypertrophy. (AU)

Gut microbiota might mediate the benefits of high-fiber/acetate diet to cardiac hypertrophy mice.

Continuously prolonged cardiac hypertrophy results in maladaptive myocardial remodeling, which affects cardiac function and can eventually lead to heart failure. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, have been reported to be associated with cardiovascular diseases (CVD). Gut microbiota may mediate between dietary fiber and SCFA effects on cardiac hypertrophy. The mice model of isoproterenol (ISO)-induced cardiac hypertrophy was constructed and verified for physiological, functional, and fibrotic alterations in this study. Both high-fiber and acetate diet improved physiological indexes, ameliorated cardiac functions, and relieved fibrotic alterations in model mice hearts; collectively, cardiac hypertrophy in mice receiving both high-fiber and acetate diet improved. Following 16s rDNA sequencing and integrative bioinformatics, analyses indicated that both high-fiber and acetate diet caused alterations in mice gut microbiota compared with the ISO group, including OTU composition and abundance. In conclusion, high-fiber and acetate diet improve the physiological status, cardiac functions, and fibrotic alterations in ISO-induced hypertrophic mice. Besides, considering the alterations in mice gut microbiota in response to single ISO, both high-fiber and acetate diet treatment, gut microbiota might mediate the favorable benefits of both high-fiber and acetate diet on cardiac hypertrophy.

Berberine up-regulates miR-340-5p to protect myocardial ischaemia/reperfusion from HMGB1-mediated inflammatory injury.

AIMS: Myocardial ischaemia/reperfusion injury (MIRI) is a major cause of heart failure after myocardial infarction. Berberine (BBR) presents anti-inflammatory and immunosuppressive properties in many diseases. Our research looked into the therapeutic effects and mechanism of BBR in MIRI. METHODS AND RESULTS: MIRI animal and cell models were established. The mRNA and protein expressions were assessed using reverse transcription and quantitative real-time polymerase chain reaction and western blot. The haemodynamic parameters (left ventricular ejection fraction and left ventricular ejection fraction) were detected by echocardiography. The myocardial infarct size and myocardium lesion were assessed by triphenyltetrazolium chloride and haematoxylin-eosin staining. The levels of injury factors were determined by ELISA. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining was performed to analyse cell apoptosis. Dual luciferase reporter gene and RNA immunoprecipitation assays were carried out to verify the interaction between miR-340-5p and HMGB1. BBR administration could improve the haemodynamic parameters and infarct size in MIRI rats (all P < 0.05). In MIRI rat model, BBR reduced cardiomyocyte apoptosis and inflammation (all P < 0.05). BBR could promote miR-340-5p expression (0.64 ± 0.21, P < 0.05), which is lowly expressed in MIRI group (0.24 ± 0.10, P < 0.01) in compare with the sham group (0.99 ± 0.01). MiR-340-5p knockdown abolished the protective effects of BBR on H/R-treated cardiomyocytes (all P < 0.05). BBR suppressed the HMGB1/TLR4/NF-κB pathway activation in MIRI. HMGB1 functioned as the target of miR-340-5p, and its silencing reversed the effect of miR-340-5p inhibitor on BBR-treated MIRI. CONCLUSIONS: In MIRI, BBR repressed HMGB1-mediated TLR4/NF-κB signalling pathway through miR-340-5p to suppress cardiomyocyte apoptosis and inflammation.

Biodegradation of polyethylene by Meyerozyma guilliermondii and Serratia marcescens isolated from the gut of waxworms (larvae of Plodia interpunctella).

The widespread use of polyethylene (PE) causes a large amount of indigestible plastic waste. Waxworms (the larvae of Plodia interpunctella) can eat PE, but the degradation principle of PE under the action of intestinal microorganisms is still unclear, especially the insufficient research on key degradable PE strains. In this study, we fed waxworms with PE. Two strains with high PE degradation efficiency were isolated and purified, and the effects of single and microbial consortia on PE degradation were evaluated by water contact angle (WCA), FTIR, GC-MS, SEM and RT-qPCR. The results showed that Meyerozyma guilliermondii ZJC1 (MgZJC1) and Serratia marcescens ZJC2 (SmZJC2) could degrade PE. However, the degradation efficiency of the microbial consortium was higher, and the weight loss rate of PE was 15.87 %. In addition, the PE degradation products of MgZJC1 were C9H10O, C20H15NO, C28H44O3 and C16H32O2, and the PE degradation products of SmZJC2 were C16H18O, C14H18N2O7 and C31H48O6. The PE degradation products of the microbial consortium were C11H24, C19H10O, C15H32, C14H30, C16H34, C25H52 and C27H56. RT-qPCR results showed that SmZJC2 promoted PE degradation by upregulating the expression of multiple genes, such as multicopper oxidase genes (PiSm-CueO). MgZJC1 responded to carbon deficiency by upregulating the expression of multiple genes, such as key enzyme genes in the tricarboxylic acid (TCA) cycle. This study can be used to develop an efficient microbial consortium for PE degradation and provide a basis for the reuse of PE waste. It can also provide a research basis for the joint degradation of PE by microbial consortia composed of bacteria and fungi.

Ectopic Acsl6 Overexpression Partially Improves Isoproterenol-Induced Cardiac Hypertrophy In Vivo and Cardiomyocyte Hypertrophy In Vitro.

ABSTRACT: The increase in cardiac myocyte size is a critical issue in cardiac hypertrophy development. In this study, 61 differentially expressed genes between hypertrophic rats and normal controls were enriched in the positive modulation of fatty acid uptake, fatty acid metabolism and degradation, cardiac conduction, and the oxidation of carbohydrates and other processes. Acsl6 was significantly downregulated in hypertrophic rat and mouse hearts according to online data. Based on the experimental data, Acsl6 was underexpressed in ISO-induced cardiac hypertrophy mouse model and isoproterenol (ISO)-induced cardiomyocyte hypertrophy cell model. In vivo, Acsl6 overexpression partially attenuated ISO-induced increases in the cross-sectional area and cardiac hypertrophy, elevated hypertrophic markers, and caused impairment of cardiac function. In vitro, Acsl6 overexpression partially attenuated ISO-induced cardiomyocyte hypertrophy and increased hypertrophic markers. Conclusively, Ascl6 is downregulated in ISO-induced cardiac hypertrophy mouse model and ISO-induced cardiomyocyte hypertrophy cell model. Acsl6 overexpression could partially improve cardiac hypertrophy in vivo and cardiomyocyte hypertrophy in vitro, possibly through the regulation of HIF-1α/Hippo pathway.

Emerging role of m6 A modification in cardiovascular diseases.

Cardiovascular diseases (CVDs) contribute to the leading cause of death worldwide. Despite significant improvements in CVDs diagnosis and treatment, a continued effort to explore novel therapeutic strategies is urgently need. N6-methyladenosine (m6 A) RNA methylation, well known as the most prevalent type of RNA modifications, involved in RNA stability, nuclear exports, translation, and decoy, plays a crucial role in the pathogenesis of a variety of diseases, including CVDs, cancer, and drug resistance. Here, our article summarizes cellular functions of m6 A modulators and recent research progress concerning the functions and mechanisms of m6 A methylation in CVDs, in hope of providing references for exploring novel therapeutic approaches and potential biomarkers in the treatment of CVDs.

Facile synthesis of chitosan-derived maillard reaction productions coated CuFeO2 with abundant oxygen vacancies for higher Fenton-like catalytic performance.

The two shortcomings of the Fenton-like catalyst delafossite-type oxide (CuFeO2) lie in its spontaneous agglomeration and deactivation under neutral working pH. To remedy these drawbacks, novel Fenton-like catalyst chitosan-derived maillard reaction productions coated CuFeO2 with abundant oxygen vacancies (OV-CuFeO2@MRPs) was synthesized by hydrothermal method with no extra chemical reducing agent. The systemic characterization illustrated that richer oxygen vacancies and higher particles dispersion of OV-CuFeO2@MRPs contributed to better Rhodamine B (RhB) degradation under neutral pH compared to pure CuFeO2. Cooper antisite defects in OV-CuFeO2@MRPs were evidenced by X-ray powder diffraction (XRD), fourier transform infrared spectrometer (FTIR), Raman spectra and energy dispersive X-ray spectrometer (EDX) linescan. To keep the charge balance, OV-CuFeO2@MRPs should form rich oxygen vacancies, which was confirmed by X-ray photoelectron spectroscopy (XPS) and solid-state electron paramagnetic resonance spectrometer (solid-state EPR). Furthermore, the electrochemical impedance spectroscopy (EIS) analysis revealed that oxygen vacancies could improve the electron transfer. Scavenging experiments and electron spin resonance spectroscopy (ESR) analysis demonstrated that OH was main active radical during Fenton-like reaction, and the density functional theory (DFT) calculation verified that the oxygen vacancy could effectively adsorb H2O2 and elongate O-O bond of H2O2, thus promoting the activation of H2O2 into OH.

LINC00472 regulates vascular smooth muscle cell migration and proliferation via regulating miR-149-3p.

LncRNAs are one group of gene modulators functioning via several mechanisms in pathological and physiological conditions. We noted that LINC00472 expression level is elevated in atherosclerotic coronary tissues compared with normal coronary artery samples. LINC00472 is also upregulated in vascular smooth muscle cells (VSMCs) induced by TNF-α and PDGF-BB. Ectopic expression of LINC00472 induced VSMC migration and proliferation. The predicted binding sequence between miR-149-3p and LINC00472 was analyzed by LncBase Predicted. Overexpression of miR-149-3p decreases the luciferase activity of wild-type reporter plasmid, but not the mutant one. Ectopic expression of LINC00472 suppresses the expression of miR-149-3p in VSMCs. Furthermore, we demonstrated that miR-149-3p expression is decreased in atherosclerotic coronary tissues. MiR-149-3p was downregulated in VSMCs induced by TNF-α and PDGF-BB. Overexpression of LINC00472 induces VSMC migration and proliferation via regulating miR-149-3p. These data suggested that LINC00472 acts a critical role in the migration and proliferation of VSMCs partly via modulating miR-149-3p.

CircPAN3 ameliorates myocardial ischaemia/reperfusion injury by targeting miR-421/Pink1 axis-mediated autophagy suppression.

Cardiovascular diseases are considered the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is recognized as a critical risk factor for cardiovascular diseases. Although increasing advances have been made recently in understanding the mechanisms of I/R injury, they remain largely unknown. In this study, we found that the expression of circPAN3 (circular RNA PAN3) was decreased in a mouse model of myocardial I/R. Overexpression of circPAN3 significantly inhibited autophagy and alleviated cell apoptosis of cardiomyocytes, which was further verified in vivo by decreased autophagic vacuoles and reduced myocardial infarct sizes. Moreover, miR-421 (microRNA-421) was identified as a downstream target involved in circPAN3-mediated myocardial I/R injury. Additionally, miR-421 could negatively regulate Pink1 (phosphatase and tensin homologue-induced putative kinase 1) via a direct binding relationship. Furthermore, the mitigating effects of circPAN3 overexpression on myocardial I/R injury by suppressing autophagy and apoptosis were abolished by knockdown of Pink1. Our findings reveal a novel role for circPAN3 in modulating autophagy and apoptosis in myocardial I/R injury and the circPAN3-miR-421-Pink1 axis as a regulatory network, which might provide potential therapeutic targets for cardiovascular diseases.

circPAN3 exerts a profibrotic role via sponging miR-221 through FoxO3/ATG7-activated autophagy in a rat model of myocardial infarction.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Cardiac fibrosis is the scarring process occurs commonly with CVDs impairing the function and structure of heart. Herein, we investigated the role of circPAN3 in the pathogenesis of cardiac fibrosis. METHODS: A rat myocardial infarction (MI) model was constructed to evaluate the role of circPAN3. Expression of circPAN3 in MI was determined, and si-circPAN3 was applied to verify its profibrotic effects. With an in vitro model, cardiac fibroblasts were stimulated by transforming growth factor beta 1 (TGFß1). Immunofluorescent staining was employed to assess the fibrosis-related markers, as well as autophagy activity. CCK-8 and transwell assays were performed to determine cell proliferation and migration. Luciferase reporter assay and RNA pull-down were subjected to verify the interaction of circPAN3/miR-221. The enrichment of FoxO3 on the promoter region of ATG7 was detected using CHIP assay. RESULTS: Elevated circPAN3 was found in rat MI heart tissue, of which knockdown attenuated cardiac fibrosis after MI. In an in vitro model exposing with TGFß1, increasing cell proliferation and migration were observed, whereas these effects were abolished by circPAN3 knockdown, as well as autophagy activity. miR-221 was identified as a target to be involved in circPAN3-mediated cardiac fibrosis after MI. miR-221 negatively regulated FoxO3, thus causing the inhibition of ATG7 transcription. The regulatory network of circPAN3/miR-221/FoxO3/ATG7 in cardiac fibrosis was further determined in vivo. CONCLUSION: circPAN3 exhibited profibrotic effects during autophagy-mediated cardiac fibrosis via miR-221/FoxO3/ATG7 axis, which may serve as potential biomarkers for cardiac fibrosis therapeutics.

Association between depressive symptoms and arterial stiffness: a cross-sectional study in the general Chinese population.

OBJECTIVES: To determine the independent relationship between depressive symptoms and arterial stiffness in the general Chinese population, and to explore possible interactive factors in the relationship. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: Consecutive participants who received routine health physical examination in an affiliated hospital of a comprehensive university in Hunan Province, China, between September 2013 and March 2014 were examined. After exclusion of subjects not meeting the criteria, a total of 1334 subjects aged 22-77 years were recruited for final analysis. MEASURES: The Patient Health Questionnaire-9 was employed to assess the degree of depressive symptoms: 0-4 no depressive symptoms, 5-9 mild depressive symptoms and 10-27 moderate to severe depressive symptoms. Brachial-ankle pulse wave velocity (baPWV) was measured to determine arterial stiffness. RESULTS: There was a slight increase in baPWV across elevated degrees of depressive symptoms (p=0.025). Multivariate linear regression analysis revealed that mild depressive symptoms and moderate to severe depressive symptoms were independently associated with baPWV compared with no depressive symptoms after adjusting for baseline confounders (beta-coefficient: 40.3, 95% CI 6.6 to 74.1; beta-coefficient: 87.7, 95% CI 24.0 to 151.5, respectively). Further stratified analyses indicated that the relationship between degree of depressive symptoms and baPWV was predominant in subjects who had normal or normal-high blood pressure, or combined with hypertension (p for interaction=0.016), or in subjects with diabetes mellitus (p for interaction=0.004), examined in multivariate linear regressions. In addition, after adjustment, a significant association between moderate to severe depressive symptoms and baPWV was also found in female subjects younger than 60 years, although the interactive effect was not significant (p for interaction=0.056). CONCLUSIONS: Depressive symptoms are independently associated with arterial stiffness, especially in subjects whose blood pressures are beyond the optimal range and combined with diabetes mellitus.

Dynamic Responses of the Caudal Neurosecretory System (CNSS) Under Thermal Stress in Olive Flounder (Paralichthys olivaceus).

Temperature is a critical environmental factor that affect most biological and physiological processes in fish. The caudal neurosecretory system (CNSS) is unique to fish and is proved to maintain homeostasis during seasonal alterations. However, the dynamic expression and secretion pattern of its major hormones, corticotrophin-releasing hormone (CRH), urotensin I (UI), and urotensin II (UII), and their response to thermal stress has not been studied. CRH, UII and cortisol in plasma, gene expression levels of CRH, UI, and UII in the CNSS of olive flounder (Paralichthys olivaceus) were therefore characterized. UI- and UII-positive Dahlgren cells, as well as cell proliferation in the CNSS, were also quantified. The results showed that plasma cortisol and CRH were increased in both low temperature (LT) and high temperature (HT) groups. However, there was no difference in plasma UI and UII during thermal stress. In CNSS, CRH, UI, and UII mRNA levels were all significantly elevated in response to acute hypothermal stress and recovered back to the control (normal) level after 8 days of adaptation. During hyperthermal challenge, gene expression of CRH and UI only significantly increased after 8-days of transfer but no change in UII was observed. We also demonstrated an increasing percent of UI-positive Dahlgren cells in the CNSS of 8-days hyperthermal stressed fish. However, no BrdU-labeled Dahlgren cells were found among the three treatment groups. Collectively, our results demonstrate that the CNSS is subjected to dynamic responses under thermal stress and expands upon the role of the CNSS in thermoregulation. The dynamic responses of hormone levels and the gene expression of CRH, UI and UII in CNSS are all involved in the process of hyper- or hypo-thermal stress and adaptation.

Beta 2-Microglobulin and the Severity of Coronary Stenosis in Patients With Acute Coronary Syndrome.

BACKGROUND: Previous studies have shown that beta 2-microglobulin (B2M) could predict all-cause mortality and cardiovascular mortality in various groups of people. However, the relationship between B2M and severity of coronary stenosis in patients with acute coronary syndrome has not been established. METHODS: We enrolled 872 consecutive patients admitted with acute coronary syndrome in our study. All participants underwent coronary angiography examination or stent implantation after admission. The severity of coronary stenosis was assessed by Gensini score and the presentation of triple-vessel disease. B2M and other biochemical parameters were measured. All subjects were divided into quartiles of B2M. Multivariate linear regression and logistic regression were applied in the analysis. RESULTS: Gensini score and the prevalence of triple-vessel disease were elevated in accordance with increasing B2M quartiles (p=0.002 and p<0.001, respectively). Multivariate regression showed diabetes (p=0.031), high-sensitivity C-reactive protein (hs-CRP, p=0.043) and B2M (p=0.006) were positively correlated with Gensini score. Logistic regression analysis revealed that the crude and fully adjusted odds ratios of triple-vessel disease were 2.34 (95% CI: 1.58-3.46) and 1.97 (95% CI: 1.14-3.40) in the fourth quartile of B2M compared with the first quartile, respectively. However, no interactive relationships were found in subgroup analysis by estimated glomerular filtration rate or hs-CRP in the above associations, neither in the distribution of Gensini score (p for interaction>0.05 for both). CONCLUSION: Our data indicated that B2M was an independent risk factor of coronary stenosis in patients with acute coronary syndrome.

Correlations of DAPT score and PRECISE-DAPT score with the extent of coronary stenosis in acute coronary syndrome.

Dual antiplatelet therapy (DAPT) score and PRECISE-DAPT score were recommended for decision making of optimal DAPT in discriminating the risk of thrombosis and bleeding. But the relationships between 2 scoring tools with the extent of coronary stenosis have not been established.We retrospectively enrolled 359 patients of acute coronary syndrome (ACS) who received percutaneous coronary intervention. Both DAPT score and PRECISE-DAPT score were calculated, and patients were divided by their recommended cut-offs. Gensini score and triple-vessel disease (3-VD) were chosen to evaluate the severity of coronary stenosis.Overall, 54.9% and 10.0% of the patients had higher DAPT score (≥2) or PRECISE-DAPT score (≥25). Patients with higher DAPT score had increased stent counts, total length of stents, Gensini score, and proportion of 3-VD, but decreased minimum diameter of stent. But these differences were not found in PRECISE-DAPT subgroups. When divided into quartiles of both scoring systems, the highest Gensini score and proportions of 3-VD were found in the fourth quartile of both DAPT score and PRECISE-DAPT score. Moreover, both DAPT score and PRECISE-DAPT score were independent risk factors of Gensini score after adjustment (P < .001 and P = .047). Furthermore, an increase of 1 point of DAPT score and 5 points of PRECISE-DAPT score resulted by 51% (odds ratios [OR]: 1.51, 95% confidence interval [CI]:1.19-1.91, P = .001) and 34% (OR: 1.34, 95% CI: 1.11-1.62, P = .003) increase in risk of 3-VD after adjustment.Both DAPT score and PRECISE-DAPT score were independently associated with the degree of coronary stenosis in patients with ACS.