The crucial relationship between miRNA-27 and CSE/H2S, and the mechanism of action of GLP-1 in myocardial hypertrophy.

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H2S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H2S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.

Methanol-Dependent Carbon Fixation for Irreversible Synthesis of d-Allulose from d-Xylose by Engineered Escherichia coli.

d-Allulose is a rare hexose with great application potential, owing to its moderate sweetness, low energy, and unique physiological functions. The current strategies for d-allulose production, whether industrialized or under development, utilize six-carbon sugars such as d-glucose or d-fructose as a substrate and are usually based on the principle of reversible Izumoring epimerization. In this work, we designed a novel route that coupled the pathways of methanol reduction, pentose phosphate (PP), ribulose monophosphate (RuMP), and allulose monophosphate (AuMP) for Escherichia coli to irreversibly synthesize d-allulose from d-xylose and methanol. After improving the expression of AlsE by SUMO fusion and regulating the carbon fluxes by knockout of FrmRAB, RpiA, PfkA, and PfkB, the titer of d-allulose in fed-batch fermentation reached ≈70.7 mM, with a yield of ≈0.471 mM/mM on d-xylose or ≈0.512 mM/mM on methanol.

[Impact of shengmal injection on changes of immunological function in patients after cardiopulmonary bypass].

OBJECTIVE: To study the impact and mechanism of Shengmai Injection (SMI) on the immunological function changes after cardiopulmonary bypass. METHODS: Forty patients with rheumatic heart valve disease were selected and assigned randomly to two groups: 20 in the control group and 20 in the SMI group. Peripheral blood samples were taken at various time points, i.e. 3 days before operation (T1), 10 min after terminal of CPB (T2), the first (T3), third (T4), and seventh (T5) day after operation, for counting white blood cell (WBC), neutrophils and lymphocytes; percentage of T lymphocytes (CD3+ mononuclear cells) and its subsets (CD4+ and CD8+) to calculate CD4+/CD8+ ratio; and the serum content of immunoglobulins (IgG, IgA, IgM) as well as serum concentration of interleukin-8 (IL-8) and interleukin-10 (IL-10) were assayed. RESULTS: Compared with the control group, in the SMI group, WBC and neutrophil count were lower at T2 (P < 0.01); percentages of CD3+ and CD4+ lower at T4 and T5 (P < 0.05 or P < 0.01); percentage of CD8+ higher at T2 to T5 (P < 0.05 or P < 0.01); CD4+/CD8+ ratio lower at T3 to T5 (P < 0.05 or P < 0.01); IgG lower at T2 (P < 0.05); IgA higher at T3 (P < 0.05); IgM higher at T3 to T5 (P < 0.05); IL-8 lower at T2 to T4 (P < 0.05); and IL-10 higher at T2 (P < 0.05). CONCLUSION: Application of SMI in the perioperative period can enhance the humoral immunity and inhibit the cellular immunity after CPB, it could also reduce the systemic inflammatory reaction and improve the prognosis of patients.

[Comparative study on the immunogenicity of human homologous cardiac valve and great artery homograft cryopreserved with liquid nitrogen].

OBJECTIVE: To study the differences on the immunogenicity of the leaflets, arterial wall and myocardium of conduit valved homograft (CVH) cryopreserved with liquid nitrogen. METHODS: Mono-cell suspension of leaflets cells and arterial cells of CVH were respectively co-cultured with human lymphatic cells whose blood groups were the same with that of CVH donors. Expressive levels of CD25 and HLA-DR of these lymphatic cells were detected by flow cytometry in the different cultural duration and compared with that of lymph cells alone cultured (comparative group). RESULTS: The immunogenicity of CVH artery walls was more severe than that of CVH leaflets, and expressive level of whose CD25 and HLA-DR was higher. The immunogenicity of CVH myocardium was not studied because the myocardial cell suspension were not be acquired in this study. CONCLUSION: It is proved that in vitro experimental study that the immunogenicity of arterial walls of cryopreserved CVH is more severe than that of leaflets.