The randomized clinical trial results of the anxiety treatment in patients with somatoform dysfunction and neurotic disorders.

The existing treatments for somatoform dysfunction (SfD), reaction to severe stress (RSS), and adjustment disorders (AjD) are insufficiently effective and safe. Anxiolytic drug Tenoten proved effective in clinical trials (CT). The aim of this multicenter double-blind placebo-controlled randomized CT was to investigate the safety and efficacy of Tenoten in the treatment of anxiety in adults with SfD, RSS, AjD and other neurotic disorders (oNDs). 390 adult patients with SfD, RSS and AjD or oNDs with the Hospital Anxiety and Depression scale-anxiety (HADS-A) score ≥ 11 were randomized into 4 groups (n = 127 in Tenoten group 1 (4 tablets/day); n = 131 in Tenoten group 3 (8 tablets/day), n = 132 in combined Placebo group 2 + 4). The changes from baseline in the mean Hamilton Anxiety Rating Scale (HAM-A) score in groups 1 and 3 after 12 weeks were the primary outcome. The decrease of the HAM-A score from 18.81 ± 5.81 to 7.26 ± 4.63 (in group 1) and from 18.38 ± 4.3 to 6.40 ± 4.02 (in group 3) was observed post-treatment (pgroup 1/placebo = 0.0055, pgroup 3/placebo < 0.0001). Overall, 46 adverse events (28 in the Tenoten groups and 18 in the Placebo) were reported without any difference between the study groups. Tenoten performed significantly more effective than placebo in the anxiety treatment of adults with SfD, RSS, AjD and oNDs (clinicaltrials.gov NCT03036293).

Prediction of miRNA interaction with mRNA of stroke candidate genes.

BACKGROUND: The role of miRNA in tissue affected by stroke is actively studied, but it remains unclear which miRNAs and target genes are involved in the development of stroke. METHODS: The MirTarget program defines the following features of a miRNA binding to a mRNA: the binding start site, the location of the binding site in mRNA, the free energy of a miRNA binding with a mRNA, and the interaction schemes of miRNA and mRNA. RESULTS: The interaction of 6565 miRNAs with mRNAs of stroke candidate genes was determined. The association of the mRNAs of stroke candidate genes with miRNAs depends on the level of gene expression. Some highly expressed candidate genes are targets of miR-619-5p and miR-5095, which have binding sites located on overlapping mRNA nucleotide sequences (clusters). miR-619-5p and miR-5095 bind to mRNA of 15 genes. Clusters for the binding of miR-1273f,d,e are in mRNAs of highly expressed genes. The start sites of miR-1273d and miR-1273e binding in all clusters are in sequences with one and ten nucleotides, respectively. The clusters of multiple miR-574-5p and ID00470.5p-miR binding sites and the clusters of the miR-466, ID01030.3p-miR, and ID00436.3p-miR binding sites are in mRNAs of some genes expressed at low levels. CONCLUSION: The organization of miRNA binding sites into clusters reduces the length of mRNA and creates competition between miRNAs for binding to mRNA of a target gene. The characteristics of miRNA associations with target genes can be used to recommend markers for a diagnosis of stroke.