Siberian State Medical University

Chelidonic acid (ChA) is small molecule capable of inducing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and the formation of mineralized bone matrix (MBM) both in vitro and in vivo. However, the molecular mechanisms underlying these effects are unknown. Therefore, in silico modelling of potential molecular targets of ChA was performed. ChA was isolated from Saussurea controversa. The ability of ChA to induce in vitro differentiation MSCs into osteoblasts synthesizing MBM was detected using alizarin red staining. ChA osteogenic activity was studied in mice by in situ test of ectopic osteogenesis, using the subcutaneous implantation of syngeneic bone marrow on the calcium phosphate coated titanium plates. DIGEP-Pred web service was used to simulate in silico the effect of ChA on gene expression, and overrepresentation analysis to search for common ontologies and pathways. ChA linearly increased the number of single (R² = 0.92, p = 0.039) and the total areas of MBM sites (R² = 0.96, p = 0.019) in a 21-day MSC culture. Oral administration of ChA led to two to three times improved bone and bone marrow formation in situ. In silico modelling identified 306 genes (including 7 calcium import genes) and 9 signalling pathways potentially involved in ChA osteogenic effect and calcium metabolism in MSCs. In silico analysis revealed a list of key signalling pathways and genes for calcium influx into MSCs and their differentiation into osteoblasts as the first target candidates for studying real gene expression and molecular mechanisms of the ChA osteogenic effects.

DYNC1H1 encodes the heavy chain of dynein 1, a protein that plays a critical role in intracellular transport and is also involved in neurogenesis, bipolar spindle apparatus formation, and interaction with certain regulatory proteins. Many variants of the gene are described in various neuromuscular, psychoneurological, congenital abnormalities, and malignancies. In this clinical case, the correlation of clinical manifestations with molecular genetic changes of the DYNC1H1 gene was evaluated. A variant was identified and presented de novo in the linker domain of the protein in a patient with abnormalities of brain development (pachygyria of the temporal and frontal lobes, polymicrogyria of the occipital lobes, cerebellar agenesis), polydactylitis, mental development disorder, and involvement of the neuromuscular system, as well as congenital cataracts. In this case, a new feature is described — polydactyly — not previously described in the variant c.4868G>A (p.Arg1623Gln), which expands the range of clinical manifestations and can contribute to the understanding of the mechanisms of phenotypic heterogeneity, as well as the development of optimal diagnostic algorithms.

Objective. To conduct a comparative analysis of EEG spectral power indicators in patients with alcoholism with- or without exogenous organic brain disease. Material and methods. An analysis of 119 EEG of patients with alcohol dependence was carried out. The presence of exogenous organic brain disease in patients was assessed retrospectively (through anamnesis). The EEG signals received from 16 electrodes were first divided into 3 frequency spectra (i.e. theta, alpha and beta), then the values of absolute spectral power were calculated, and then they were reordered, combined and topographically transferred to a spectral map. Data analysis was carried out in 5 different ways: electrode analysis, analysis based on cortical regions, lateralization, antero-posterior locus and throughout the whole cortex. Results. In the group of alcohol-dependent patients with comorbid exogenous organic brain damage, significantly (p<0.05) lower values of the spectral power of alpha activity on the Fp2, F3, F4, C3 and C4 electrodes as well as higher values of the spectral power of beta activity on the F8, T5 and T6 electrodes compared with the group of patients with «pure» alcohol dependence were observed. The intergroup data analysis, taking into account the topographic distribution, revealed significant differences in the spectral power of alpha activity in the prefrontal (F=4.201; p=0.043), frontal (F=3.951; p=0.049), central (F=4.033; p=0.047) and parietal (F=3.926; p=0.049) regions, as well as beta activity in the temporal region (F=5.656; p=0.019) of the cerebral cortex. Compared with patients suffering only from alcohol dependence, the group of patients with alcohol dependence and exogenous organic brain damage had significantly lower spectral power of alpha activity on the left (F=5.329; p=0.019) and on the right (F=5.191; p=0.027), as well as in the anterior locus (F=3.975; p=0.049). Conclusion. The results clearly indicate that the presence of exogenous organic brain damage in patients with alcohol dependence is accompanied by a change in the spectral power of the EEG mainly in the alpha frequency range.