Background Coronary artery disease (CAD) is associated with gut microbiota alterations in different populations. Gut microbe-derived metabolites have been proposed as markers of major adverse cardiac events. However, the relationship between the gut microbiome and the different stages of CAD pathophysiology remains to be established by a systematic study. Results Based on multi-omic analyses (sequencing of the V3-V4 regions of the 16S rRNA gene and metabolomics) of 161 CAD patients and 40 healthy controls, we found that the composition of both the gut microbiota and metabolites changed significantly with CAD severity. We identified 29 metabolite modules that were separately classified as being positively or negatively correlated with CAD phenotypes, and the bacterial co-abundance group (CAG) with characteristic changes at different stages of CAD was represented by Roseburia , Klebsiella , Clostridium IV and Ruminococcaceae . The result revealed that certain bacteria might affect atherosclerosis by modulating the metabolic pathways of the host, such as taurine, sphingolipid and ceramide, and benzene metabolism. Moreover, a disease classifier based on differential levels of microbes and metabolites was constructed to discriminate cases from controls and was even able to distinguish stable coronary artery disease from acute coronary syndrome accurately. Conclusion Overall, the composition and functions of the gut microbial community differed from healthy controls to diverse coronary artery disease subtypes. Our study identified the relationships between the features of the gut microbiota and circulating metabolites, providing a new direction for future studies aiming to understand the host–gut microbiota interplay in atherosclerotic pathogenesis. Electronic supplementary material The online version of this article (10.1186/s40168-019-0683-9) contains supplementary material, which is available to authorized users.

J.Y. performed mass spectrometry and provided intellectual support for redox subject. J.Y. and K.-S.C. provided technical support for redox modification examination. J.-F.P. performed real-time luciferase assays with the help from D.J. and N.L.. E.-E.Z. conceived LumiCycle design and provided intellectual support for the project. J.-F.P. prepared the illustrations and wrote the manuscript under the guidance of H.-Z.C. and D.-P.L.. J.-H.Q. and J.-M.C. contributed to revision of characters. All authors contributed to data analysis and reviewed the manuscript. H.-Z.C. and D.-P.L. supervised the study.

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Background Although surgical resection provides a cure for patients with intrahepatic cholangiocarcinoma (ICC), the risk of mortality and recurrence remains high. Several biomarkers are reported to be associated with the prognosis of ICC, including Beclin-1, ARID1A, carbonic anhydrase IX (CA9) and isocitrate dehydrogenase 1 (IDH1), but results are inconsistent. Therefore, a histopathological retrospective study was performed to simultaneously investigate the relationship of these four potential biomarkers with clinicopathological parameters and their prognostic values in patients with ICC. Methods A total of 113 patients with ICC were enrolled from Cancer Hospital of Chinese Academy of Medical Sciences between January 1999 and June 2015. The expression of Beclin-1, ARID1A, IDH1 and CA9 were determined by immunohistochemical staining. The prognostic values of the four biomarkers were analyzed by Cox regression and the Kaplan-Meier method. Results Beclin-1, ARID1A, CA9 and IDH1 were highly expressed in ICC tumor tissues. Higher mortality was positively associated with Beclin-1 expression (HR = 2.39, 95% CI = 1.09–5.24) and higher recurrence was positively associated with ARID1A expression (HR = 1.71, 95% CI = 1.06–2.78). Neither CA9 nor IDH1 expression was significantly associated with mortality or disease recurrence. Kaplan-Meier survival curves showed that ICC patients with higher Beclin-1 and ARID1A expression had a lower survival rate and a worse recurrence rate than patients with low Beclin-1 and ARID1A expression ( p < 0.05). Conclusions High Beclin-1 and ARIDIA expression are strongly associated with poor prognosis in ICC patients, and thus Beclin-1 and ARID1A should be simultaneously considered as potential prognostic biomarkers for ICC patients. Electronic supplementary material The online version of this article (10.1186/s12885-019-5429-3) contains supplementary material, which is available to authorized users.

Objective: The study objective was to compare the onset of platelet inhibition (inhibition of platelet aggregation) between ticagrelor 90 mg twice per day and clopidogrel 75 mg once per day in patients receiving coronary artery bypass grafting.Methods: In a single-center, randomized, open-label study, 140 patients receiving coronary artery bypass grafting were randomly assigned to the aspirin þ ticagrelor group or the aspirin þ clopidogrel group in a 1:1 ratio. Participants in the aspirin þ ticagrelor group took aspirin 100 mg once per day and ticagrelor 90 mg twice per day. Participants in the aspirin þ clopidogrel group took aspirin 100 mg once per day and clopidogrel 75 mg once per day. Platelet function was determined before study treatment (0 hours); at 2 hours, 8 hours, 24 hours, and 72 hours after medication; and during follow-up at 30 days after surgery.

Circulating proteomic signatures of age are closely associated with aging and age-related diseases; however, the utility of changes in secreted proteins in identifying therapeutic targets for diseases remains unclear. Serum proteomic profiling of an age-stratified healthy population and further community-based cohort together with heart failure patients study demonstrated that circulating C-C motif chemokine ligand 17 (CCL17) level increased with age and correlated with cardiac dysfunction. Subsequent animal experiments further revealed that Ccll7-KO significantly repressed aging and angiotensin II (Ang II)–induced cardiac hypertrophy and fibrosis, accompanied by the plasticity and differentiation of T cell subsets. Furthermore, the therapeutic administration of an anti-CCL17 neutralizing antibody inhibited Ang II–induced pathological cardiac remodeling. Our findings reveal that chemokine CCL17 is identifiable as a novel therapeutic target in age-related and Ang II–induced pathological cardiac hypertrophy and heart failure.

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Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene (PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type (WT) control. The same protective tendency was also observed with an Apoe / background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.cardiac hypertrophy, fibrosis, paraoxonase gene cluster, angiotensin II Citation: