Bulletin of Experimental Biology and Medicine最新文献

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).

Screening of cell surface markers of three glioma cell lines (astrocytoma 1321N1, glioblastoma T98g, and glioblastoma astrocytoma U373 MG) was performed. Glioma cells expressed common mesenchymal cell markers, although the expression levels varied between the cell lines. The expression of proneural markers and glioma cancer stem cell markers was very low and also varied. Induction of differentiation towards the mesodermal cell lineages showed effective adipogenic and osteogenic differentiation for only the U373 MG cell line, while the 1321N1 and T98g lines demonstrated weak adipogenic potential and failed to undergo osteogenic differentiation. The obtained results point to the intratumor phenotypical heterogeneity of cells in gliomas and to the differences between the three studied types of gliomas with regard to the content of cells with mesenchymal phenotype.

It was found that 28-day immobilization stress in male Wistar rats leads to significant increase in the serum concentrations of proinflammatory cytokines IL-1β, IL-6, IFNγ, and monocyte chemoattractant protein-1 (MCP-1) and a decrease in the content of anti-inflammatory IL-10, as well as the ratio IL-1β/IL-10, IL-6/IL-10, and IFNγ/IL-10 compared to non-stressed animals. Administration of the heptapeptide tuftsin-Pro-Gly-Pro produced a corrective effect on cytokine concentrations under stress conditions: at a dose of 750 μg/kg, the peptide decreased the concentrations of IL-1β, IFNγ, and MCP-1 and cytokine ratios (IL-1β/IL-10 and IFNγ/IL-10), while at a dose of 250 μg/kg, it increased IL-10 levels and decreased IL-6/IL-10 and IFNγ/IL-10 ratios.

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 effect of the selective μ₂-opioid receptor agonist endomorphin-1 in reperfusion injury in male Wistar rats was studied in vivo and in vitro. The in vivo experiment included coronary artery occlusion (45 min) and reperfusion (120 min); in in vitro experiments, 45-min global ischemia of the isolated rat heart was followed by 30-min reperfusion. Endomorphin-1 was administered intravenously 5 min before in vivo reperfusion (at a dose 50 μg/kg) or added to the perfusion solution at the onset of reperfusion of the isolated heart (in a concentration of 152 nmol/liter). In vivo endomorphin-1 reduced the infarct size by 33% compared to the control group. In experiments on isolated heart, endomorphin-1 improved the contractile function during reperfusion and reduced the creatine kinase level in the coronary effluent. Hence, stimulation of cardiac μ₂-opioid receptors increases heart tolerance to the pathogenic effects of reperfusion.

The dynamics of heart rate variability (HRV) during acute stress was studied in male nonlinear rats that received single injection of serotonin (200 μg/kg) or dopamine (60 μg/kg), regular (4-fold) injections of central serotonin receptor blockers (ketanserin and granisetron, 0.1 mg/kg each) or central dopamine receptor blockers (0.1 mg/kg SCH-23390 and 10 mg/kg sulpiride), as well as a combination of central receptor blockers with the administration of serotonin or dopamine, respectively. During stress against the background of serotonin receptors blockade, a weak tachycardia, low stress index, high rhythm variability, especially in the low-frequency range were recorded; against the background of dopamine receptors blockade, increased reactivity to stress at high HR, an initial increase in the stress index, and a decrease in rhythm variability, followed by an increase in the proportion of very low frequency waves in the spectrum were revealed. Serotonin and dopamine, by stimulating peripheral receptors, predominantly weakened stress-induced changes in HRV (especially serotonin), but in combination with blockade of the corresponding central receptors contributed to maintaining tachycardia, reduced rhythm variability, and potentiated the effects of blockers in relation to stress induced changes in the wave structure of the HRV spectrum. We believe that central and peripheral serotoninergic and dopaminergic structures are involved in the formation of HRV by modulating the activity of components of the autonomous and central circuits of HR regulation, respectively.

The problem with modern nerve conduits is inability to transmit nerve impulses to the distal part of the damaged nerve. Cationic conductivity is a necessary characteristic of the nerve conduit ensuring effective regeneration of the peripheral nerves. We performed a functional assessment of the regeneration of rat sciatic nerve using a nerve conduit based on an ion-exchange membrane. A sciatic nerve defect was experimentally simulated in Wistar rats with further implantation of the LF-4SK membrane. On days 60 and 90 after surgery, the sciatic functional index and the ratio of the shin girth of the operated limb to the intact limb were calculated; on day 90, an electrophysiological assessment of nerve recovery was carried out. The results of the study showed that the conduit based on the LF-4SK membrane optimizes the functional recovery of the sciatic nerve defect.

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 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.

The development of chronic heart failure (CHF) was induced in 24-month-old male Wistar rats weighing 550-600 g by 4 subcutaneous injections of isoproterenol hydrochloride (ISO) at a dose of 10 mg/kg with 3-day intervals. The control group received injections of saline. The rats were euthanized 60 days after the last ISO/saline injection. The mortality rate in the group of rats with CHF was 30%. Histological studies showed morphological changes in the myocardium, kidneys, and lungs typical of CHF. The presented scheme of ISO administration can be used for modeling CHF in 24-month-old rats.