Bulletin of Experimental Biology and Medicine最新文献

Highly specialized gap junctions play an important role in the interaction between endothelial (EC) and multipotent mesenchymal stromal cells (MSC). Inhibition of gap junctions with a specific inhibitor carbenoxolone attenuates the effects of the medium conditioned by MSC-EC co-culture on proliferation and migration of cultured EC. In conditioned medium from co-culture, the levels of angiogenic mediators (VEGF-A, FGF-2, MCP-1, etc.) were decreased, which apparently determines lower angiogenic effect of the conditioned medium on the growth of the vascular network in the chorioallantois membrane of quail embryo in ovo. Suppression of communication through gap junctions in associations of MSC and EC, the structural and functional units of physiological and reparative angiogenesis, can directly reduce the level of proangiogenic mediators in the microenvironment, which, in turn, can help to control the regulation of vascular function in pathologies.

Alzheimer's disease was induced in female Wistar rats by bilateral injection of β-amyloid fragment 1-42 into the hippocampal region. After 8 weeks, ensheathing cells of the olfactory mucosa were transplanted into the hippocampus at the same stereotactic coordinates. These cells survived for 8 weeks; large clusters of cells were observed on week 4. On weeks 3-5 after transplantation of ensheathing cells, experimental animals demonstrated a significant cognitive improvement (memory and spatial orientation). The obtained results create prerequisites for further studies of ensheathing cells as a potential cell product for personalized therapy of Alzheimer's disease.

This work presents the method of synthesis and physicochemical characterization of isothiourea and cinnamic acid original derivative α-cyano-4-hydroxycinnamate 1-cyclohexanoy-l-2-ethylisothiourea (T1114). In studies of the cytotoxic and antitumor activity of T1114, it has been found that the combination in one molecular structure of NOS-inhibitory fragment (1-cyclohexanoyl-2-ethylisothiourea) and a fragment inhibiting monocarboxylate lactate transporters (MCT) (α-cyano-4-hydroxycinnamic acid) does not modify the cytotoxic activity of bifunctional NOS/MCT-inhibitor T1114 in vitro. But in vivo inhibition of NOS and MCT is able to realize effects on the tumor microenvironment and hypoxic tumor cells. Such structural and functional modification has significantly extended the antitumor activity of the new NOS/MCT inhibitor. The bifunctional compound not only realized a more pronounced antitumor effect, but also prevented the development of hypoxic adaptation in solid Ehrlich carcinoma and acquired the ability to overcome the resistance of mouse cervical cancer (RShM-5). Therefore, the combination of NOS-inhibitory, anti-vasculogenic and hypoxia-oriented toxic effects can create new opportunities in antiangiogenic therapy of malignant neoplasms.

In an experiment on Wistar rats, a Heymann's active nephritis model was reproduced. After the chronic course of the disease was confirmed, we compared the effectiveness of single systemic and local transplantation of allogeneic cultured stromal cells of the mononuclear fraction of the bone marrow. Both methods of cell therapy reduced clinical manifestations of active Heymann's nephritis: proteinuria decreased and glomerular filtration rate increased 30 days after cell administration. At the histological level, signs of the inflammatory process manifested in an increase in the number of CD68⁺ cells. Thus, in the case of autoimmune glomerulonephritis, two transplantation methods provide a comparable level of correction of functional disorders in Heymann's active nephritis model.

We studied the association of polymorphisms in the aminopeptidase N gene (ANPEP) with the development of diabetic retinopathy and nephropathy in patients with type 2 diabetes mellitus (T2DM). DNA samples from T2DM patients (n=1425) were genotyped for 23 single nucleotide polymorphisms (SNPs) using the MassARRAY system. Associations of SNP rs13380049 of the ANPEP gene with a lower risk of diabetic retinopathy (OR=0.54, 95%CI 0.36-0.82, p=0.0032) and nephropathy (OR=0.66, 95%CI 0.44-0.99, p=0.048) were found in T2DM patients. In addition, SNP rs25653 was associated with retinopathy, and polymorphisms rs6496608, rs72756574, rs9920421, and rs4932143 were associated with diabetic nephropathy. The study demonstrated the contribution of ANPEP gene polymorphisms in the determination of microvascular complications in T2DM patients.

The rheographic parameters of the segments of brachial and femoral arteries were measured in situ after a 14-day-long hindlimb unloading (HU) of rats. HU significantly increased electrical impedance Z of a segment of femoral artery indicating its constriction; in parallel, HU resulted in a decreasing trend of Z of a segment of brachial artery attesting to its dilation. In both arteries, HU significantly or as a trend decreased the swing ranges of active and passive pulsations, respectively. BP reduction during bloodletting induced transition from passive to active pulsatile mode in the femoral artery only in 33% experimental rats in contrast to 87% control ones. We suppose that degradation of active pulsatile mode is responsible for the negative influences of microgravity and weightlessness on blood circulation. The study determined the rheographic parameters that reliably reflect changes in the functional activity of arteries after chronic redistribution of hydrostatic load.

Long-term high-fat diet (HFD) promotes the formation of excess body weight and disorders of lipid metabolism and causes persistent dysbiotic changes in the intestinal microbial community. Changes in eating behavior, endocrine and immune functions of the host are associated with changes in the structure and functional activity of microbial communities. Short-term HFD may also influence the composition and function of the intestinal microbiota, but data on this issue are limited, and most papers are focused on the study of the large intestinal microbiota. The present study examined the effect of short-term HFD (4 weeks) on the structure of microbial communities in the small and large intestines of 24 mice. High-throughput metagenomic sequencing was performed on 48 samples of small and large intestine contents. It was revealed that short-term HFD in mice contributed to impaired glucose tolerance and increased the diversity of microbiota in the colon, but not of the small intestine, and also led to changes in the representation of certain microbial taxa (in particular Tenericutes and Verrucomicrobia). Furthermore, short-term HFD increased blood glucose levels compared to control mice (fed a normal diet), but did not affect lipid metabolism. The results will help to assess the contribution of environmental factors to the structure of microbial communities of the small and large intestines and may also be useful for correcting dysbiotic conditions, including when prescribing therapeutic diets (for example, a ketogenic diet).

A comparative study of oxidative stress markers (ischemia-modified albumin (IMA) and the blood serum antioxidant capacity) in normal pregnancy and preeclampsia was carried out. The IMA level and blood serum antioxidant capacity increased in the following order: healthy non-pregnant women→healthy pregnant women→patients with moderate preeclampsia→patients with severe preeclampsia (p<0.001). A significant positive correlation was revealed between blood serum antioxidant capacity and uric acid levels in all the examined groups. The results showed that oxidative stress in preeclampsia is more pronounced compared to normal pregnancy. The levels of IMA and the blood serum antioxidant capacity can be additional criteria for assessment of the severity of preeclampsia and predicting of its course.

The interrelation between the TNFα gene polymorphism and the effectiveness of the intensive phase of chemotherapy in patients with pulmonary tuberculosis, as well as the formation of diameter of the sizes of destruction cavities was studied. It was revealed that the most adverse course of the disease and a high frequency of formation of destruction cavities are associated with the GG genotype of the TNFα gene.

The reorganization of the dentate gyrus of the hippocampus and changes in mitochondrial fission were evaluated using the kainate model of temporal lobe epilepsy. In 28 days after administration of 0.5 μg kainic acid, disturbances in the distribution of neuronal precursors in the subgranular zone of the hippocampus, thickening of the granular layer, and an increase in the content of synaptophysin in the molecular layer were detected. The observed changes were accompanied by an increase in the content of mitochondrial fission regulator protein Drp1 (dynamin related protein) and modification of the mitochondrial network in granular neurons of the dentate gyrus. These observations indicate a significant role of Drp1 in pathological rearrangements of the hippocampus during epileptogenesis and allow considering it as a potential target for pharmacological agents.