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Eha is a virulence regulator associated with the replication of Edwardsiella tarda within RAW264.7 macrophages. Eha is required for the bacteria to resist the acid and oxidative stress in macrophages. We herein demonstrate that Eha regulates the resistance of this bacterium against acidification in macrophages and explain the underlying molecular mechanism. Firstly, to find an acid or oxidative condition to induce the strongest Eha activities, we constructed pMP220- Pehalac Z plasmid and inspected the lac Z expression regulated by Eha by using a β-galactosidase assay. At exposure of pH6.3 medium 2 h, whole transcriptomic profiling of the wild type and mutant were performed by RNA-sequencing. We identified 147 differentially -expressed genes (DEGs) (|log2 ratio| ≥ 1), 113 and 34 of which were significantly up- and down-regulated, respectively, in the mutant compared with the wild type. These findings were validated by qRT-PCR. A CO functional analysis revealed that these genes were divided into 25 categories, including the bacterial processing, localization, metabolism, combination, catalysis, transportation and cellular composition. Based on the KEGG database, these genes were distributed in 55 pathways, such as the two-component system, ABC transporters, and microbial metabolism. At last, the intracellular survival rates and intraphagosomal pH of wild type ET 13 and its eha mutant in bafilomycin-treated and untreated macrophages were measured. The experiment showed that Eha was involved in protecting the bacteria from the effects of acidification within macrophages. The survival rate of the wild was also higher than that of the mutant under acid stress both in vivo and in vitro (P<0.05). Overall, Eha was found to regulate 147 genes that affect bacterial metabolism and virulence, allowing the bacteria to adapt to an acidic environment. These results could be helpful for further investigations of the mechanisms by which Edwardsiella tarda survives in macrophages.

According to the results of the MACH study additional magnesium orotate therapy has shown a positive effect on life expectancy and quality of life in patients with severe forms of heart insufficiency. Both magnesium and orotate can be cardio protective. In the presented data here additional magnesium orotate therapy was tested in 11 patients with hypertensive heart disease NYHA III-IV as compared to 10 patients with hypertensive heart disease NYHA II-IV as controls. Additional magnesium orotate therapy was 4500 mg magnesium orotate daily for 1 week. NTproBNP levels decreased significantly in the magnesium orotate group versus controls (p<0.01). Under therapy quality of life improved significantly as well. Kidney function remained stable in the normal range.

In conclusion an additional therapy with magnesium orotate is safe and can be of additional benefit in hypertensive heart disease with insufficiency.

There is an improvement in quality of life and life expectancy in heart insufficiency under an additional magnesium orotate therapy.

Heart Failure (HF) remains to be a leading factor of cardiovascular morbidity and mortality. Although risk stratification of HF is promising prediction care, there are several controversies regarding choosing more optimal combinations of biomarkers and method (single versus serial measurements) of biomarker use in routine clinical practice. Growth differentiation factor-15 (GDF-15) is considered a biomarker associated with cardiac/vascular remodeling, oxidative stress, fibrosis and inflammation that were proposed to stratify HF patients at risk of death. It has been suggested that GDF-15 adding to natriuretic peptides or other conventional biomarkers (soluble ST2, cardiac troponins and galectin-3) might improve discriminative value of entire predictive models. The short communication is depicted the discussion about the perspectives of clinical use of GDF-15 in risk stratification of HF.